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A heterozygous gain‐of‐function variant in the acyl‐CoA oxidase 1 (ACOX1) gene, c.710A>G (p.Asn237Ser), is known to cause Mitchell syndrome, a very rare progressive disorder characterized by episodic demyelination, sensory polyneuropathy, and hearing loss. Only eight patients have been described so far. A single patient has been treated with intravenous immunoglobulin administration, indicating clinical improvement. In this study, we describe a 10‐year‐old girl carrying the identical mutation, who presented with progressive sensorineural deafness, visual abnormalities, skin ichthyosis, and gait ataxia from infantile age with progressive worsening and loss of walking ability by the age of 10 years. Antioxidant therapies and monthly intravenous immunoglobulin infusions showed excellent clinical results: after 1 year of treatment, the child is now able to walk, run, and jump. We emphasize the importance of early genetic diagnosis since an effective treatment is available for this rare condition. [ABSTRACT FROM AUTHOR]

Thiamine-responsive megaloblastic anemia (TRMA) syndrome is a rare syndrome with an autosomal recessive manner that develops due to a mutation in the SLC19A2gene. SLC19A2 encodes the highaffinity thiamine transport protein 1 (THTR1), which mediates the active transport of thiamine. The classical triad consists of megaloblastic anemia, sensorineural hearing loss, and non-autoimmune diabetes. Apart from this, ophthalmological, cardiological, and neurological findings have also been described. We present a case of thiamine-responsive megaloblastic anemia (TRMA) syndrome diagnosed in an adult with a novel mutation in the SLC19A2 gene. This 38-year-old female patient, a third child from a consanguineous marriage, presented with the classic TRMA triad: sensorineural deafness, megaloblastic anemia, and autoimmune diabetes. Starting thiamine treatment is essential in reducing the devel opmen t/pro gress ion of some complications; it is crucial to increase awareness of the disease and make an early diagnosis. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression and clinical significance of miR-34c and miR-29b in peripheral blood of patients with sensorineural hearing loss. Methods 140 patients with neurological deafness admitted to our hospital from June 2020 to June 2023 were included in the study group, and 40 healthy subjects were included in the control group during the same period. SNHL patients were categorized into 63 cases in the mildly deaf group, 42 cases in the moderately deaf group, and 35 cases in the severely deaf group according to their hearing impairment. The expressions of miR-34c and miR-29b were detected by qRT-PCR, and VEGF, oxidative stress (TAC, SOD, MDA), NO and Cx26 were detected. Correlation analysis was performed by Pearson test, independent risk factors for SNHL severity were calculated by logistics regression algorithm, and the predictive value of miR-34c and miR-29b on the severity of SNHL patients was evaluated by ROC curve. Results Comparing the levels of NO, TAC, SOD, and Cx26 among the four groups, severe deafness group < moderate deafness group < mild deafness group < control group (P < 0.05); comparing the levels of VEGF and MDA, severe deafness group > moderate deafness group > mild deafness group > control group (P < 0.05). Comparison of miR-34c mRNA and miR-29b mRNA expression levels among the four groups, severe deafness group > moderate deafness group > mild deafness group > control group (P < 0.05). Pearson's test showed that SNHL patients' peripheral blood miR-34c and miR-29b were positively correlated with VEGF and MDA, and were negatively correlated with NO, TAC, SOD and Cx26 (P < 0.05). negative correlation (P < 0.05). Multifactorial logistic regression analysis showed that VEGF, MDA, NO, Cx26, TAC, SOD, miR-34c, miR-29b were independent factors affecting the severity of SNHL. Conclusion miR-34c and miR-29b are overexpressed in SNHL patients and can be used as serum markers for predictive assessment of disease severity in SNHL patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: Wolfram syndrome type 1 (OMIM# 222300; ORPHAcode 3463) is an extremely rare autosomal recessive syndrome with a 25% recurrence risk in children. It is characterized by the presence of juvenile-onset diabetes mellitus (DM), progressive optic atrophy (OA), diabetes insipidus (DI), and sensorineural deafness (D), often referred to by the acronym DIDMOAD. It is a severe neurodegenerative disease with a life expectancy of 39 years, with death occurring due to cerebral atrophy. For a positive diagnosis, the presence of diabetes mellitus and optic nerve atrophy is sufficient. The disease occurs because of pathogenic variants in the WFS1 gene. The aim of this article is to present a case report of Wolfram Syndrome Type I, alongside a review of genetic variants, clinical manifestations, diagnosis, therapy, and long-term management. Emphasizing the importance of early diagnosis and a multidisciplinary approach, the study aims to enhance understanding and improve outcomes for patients with this complex syndrome. Materials and Methods: A case of a 28-year-old patient diagnosed with DM at the age of 6 and with progressive optic atrophy at 26 years old is presented. Molecular diagnosis revealed the presence of a heterozygous nonsense variant WFS1 c.1943G>A (p.Trp648*), and a heterozygous missense variant WFS1 c.1675G>C (p.Ala559Pro). Results: The molecular diagnosis of the patient confirmed the presence of a heterozygous nonsense variant and a heterozygous missense variant in the WFS1 gene, correlating with the clinical presentation of Wolfram syndrome type 1. Both allelic variants found in our patient have been previously described in other patients, whilst this combination has not been described before. Conclusions: This case report and review underscores the critical role of early recognition and diagnosis in Wolfram syndrome, facilitated by genetic testing. By identifying pathogenic variants in the WFS1 gene, genetic testing not only confirms diagnosis but also guides clinical management and informs genetic counseling for affected families. Timely intervention based on genetic insights can potentially reduce the progressive multisystem manifestations of the syndrome, thereby improving the quality of life and outcomes for patients. [ABSTRACT FROM AUTHOR]

Spiral ganglion neurons (SGNs) transmit sound signals received by hair cells to the auditory center to produce hearing. The quantity and function are important for maintaining normal hearing function. Limited by the regenerative capacity, SGNs are unable to regenerate spontaneously after injury. Various neurotrophic factors play an important role in the regeneration process. Neuritin is a neurite growth factor that plays an important role in neural plasticity and nerve injury repair. In this study, we used bioinformatics analysis to show that neuritin was negatively correlated with cochlear damage. Then, we aimed to establish a cochlear spiral ganglion-specific sensorineural deafness model in gerbils using ouabain and determine the effects of exogenous neuritin protein in protecting damaged cochlear SGNs and repairing damaged auditory nerve function. The provides a new research strategy and scientific basis for the prevention and treatment of sensorineural deafness caused by the loss of SGNs. We were discovered that neuritin is expressed throughout the development of the gerbil cochlea, primarily in the SGNs and Corti regions. The expression of neuritin was negatively correlated with the sensorineural deafness induced by ouabain. In vitro and in vivo revealed that neuritin significantly maintained the number and arrangement of SGNs and nerve fibers in the damaged cochlea and effectively protected the high-frequency listening function of gerbils. • Neuritin is mainly expressed in the cochlear spiral ganglion neurons and corti regions of gerbils. • Neuritin is significantly down-regulated in ouabain-induced sensorineural hearing loss. • Neurtin can maintain the number and connection of spiral ganglion neurons and nerve fibers. • Neurtin can effectively protect the high-frequency listening function of sensorineural hearing loss gerbils. [ABSTRACT FROM AUTHOR]

Brown-Vialetto-Van Laere (BVVL) syndrome is a disease characterized by lower cranial nerve involvement, lower and upper motor neuron extremity findings, and sensorineural deafness. Respiratory failure (the most common non-neurological finding), muscle weakness, and slurred speech are other features. Less than 100 patients have been reported in Europe in the last century. Since it is a very rare disease, there is not enough data in the literature regarding the anesthesia approach. In motor neuron diseases, there is a risk of prolonged respiratory depression with general anesthesia because neuromuscular blocking drugs can increase paralysis and muscle weakness and residual neuromuscular block may occur. However, since the etiopathogenesis of BVVL syndrome remains unclear, our general anesthesia management in two different patients with BVVL syndrome is described. [ABSTRACT FROM AUTHOR]

Introduction Thiamine-responsive megaloblastic anemia syndrome (TRMA, OMIM reference 249270), also known as Rogers' syndrome, is a rare type of anemia characterized by the triad megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus (DM). Disturbance of thiamine transport into cells results from homozygous or compound heterozygous mutations in the SLC19A2 gene. Case Report We report the case of an 8-year-old girl who presented at age 4 years with anemia. She had a combined hematological profile of microcytic and macrocytic anemia. The parents refused bone marrow aspiration and genetic diagnosis. Hemoglobin electrophoresis established the thalassemia trait. She was later confirmed to have sensorineural deafness and monogenic DM. A tentative TRMA diagnosis was based on megaloblastic anemia, sensorineural deafness, and monogenic DM triad. The patient was treated empirically with a daily dose of thiamine 200 mg; her hemoglobin level normalized, but the deafness and DM did not improve. Conclusion In routine practice, patients with TRMA must be evaluated thoroughly for other causes of megaloblastic anemia, including therapeutic thiamine trials in the presence of sensorineural deafness or DM. These patients should be followed throughout their life span both for DM and to control their response to thiamine therapy for megaloblastic anemia. [ABSTRACT FROM AUTHOR]

Abstract Background Individuals with thiamine-responsive megaloblastic anemia (TRMA) mainly manifest macrocytic anemia, sensorineural deafness, ocular complications, and nonautoimmune diabetes. Macrocytic anemia and diabetes may be responsive to high-dosage thiamine treatment, in contrast to sensorineural deafness. Little is known about the efficacy of thiamine treatment on ocular manifestations. Cases presentation Our objective is to report data from four Italian TRMA patients: in Cases 1, 2 and 3, the diagnosis of TRMA was made at 9, 14 and 27 months. In 3 out of 4 subjects, thiamine therapy allowed both normalization of hyperglycemia, with consequent insulin suspension, and macrocytic anemia. In all Cases, thiamine therapy did not resolve the clinical manifestation of deafness. In Cases 2 and 3, follow-up showed no blindness, unlike Case 4, in which treatment was started for megaloblastic anemia at age 7 but was increased to high doses only at age 25, when the genetic diagnosis of TRMA was performed. Conclusions Early institution of high-dose thiamine supplementation seems to prevent the development of retinal changes and optic atrophy in TRMA patients. The spectrum of clinical manifestations is broad, and it is important to describe known Cases to gain a better understanding of this rare disease.

Background and Objectives: Wolfram syndrome type 1 (OMIM# 222300; ORPHAcode 3463) is an extremely rare autosomal recessive syndrome with a 25% recurrence risk in children. It is characterized by the presence of juvenile-onset diabetes mellitus (DM), progressive optic atrophy (OA), diabetes insipidus (DI), and sensorineural deafness (D), often referred to by the acronym DIDMOAD. It is a severe neurodegenerative disease with a life expectancy of 39 years, with death occurring due to cerebral atrophy. For a positive diagnosis, the presence of diabetes mellitus and optic nerve atrophy is sufficient. The disease occurs because of pathogenic variants in the WFS1 gene. The aim of this article is to present a case report of Wolfram Syndrome Type I, alongside a review of genetic variants, clinical manifestations, diagnosis, therapy, and long-term management. Emphasizing the importance of early diagnosis and a multidisciplinary approach, the study aims to enhance understanding and improve outcomes for patients with this complex syndrome. Materials and Methods: A case of a 28-year-old patient diagnosed with DM at the age of 6 and with progressive optic atrophy at 26 years old is presented. Molecular diagnosis revealed the presence of a heterozygous nonsense variant WFS1 c.1943G>A (p.Trp648*), and a heterozygous missense variant WFS1 c.1675G>C (p.Ala559Pro). Results: The molecular diagnosis of the patient confirmed the presence of a heterozygous nonsense variant and a heterozygous missense variant in the WFS1 gene, correlating with the clinical presentation of Wolfram syndrome type 1. Both allelic variants found in our patient have been previously described in other patients, whilst this combination has not been described before. Conclusions: This case report and review underscores the critical role of early recognition and diagnosis in Wolfram syndrome, facilitated by genetic testing. By identifying pathogenic variants in the WFS1 gene, genetic testing not only confirms diagnosis but also guides clinical management and informs genetic counseling for affected families. Timely intervention based on genetic insights can potentially reduce the progressive multisystem manifestations of the syndrome, thereby improving the quality of life and outcomes for patients.

We present a rare manifestation of a common pathology: left sided sensorineural hearing loss secondary to subclavian steal syndrome after thoracic endovascular aortic repair for complicated acute aortic dissection. We describe the vascular physiology that can result in unilateral hearing loss and provide a brief review of subclavian steal syndrome. This case report highlights the importance of avid clinical recognition of an atypical presentation of a common vascular disease.

Background: Individuals with thiamine-responsive megaloblastic anemia (TRMA) mainly manifest macrocytic anemia, sensorineural deafness, ocular complications, and nonautoimmune diabetes. Macrocytic anemia and diabetes may be responsive to high-dosage thiamine treatment, in contrast to sensorineural deafness. Little is known about the efficacy of thiamine treatment on ocular manifestations. Cases presentation: Our objective is to report data from four Italian TRMA patients: in Cases 1, 2 and 3, the diagnosis of TRMA was made at 9, 14 and 27 months. In 3 out of 4 subjects, thiamine therapy allowed both normalization of hyperglycemia, with consequent insulin suspension, and macrocytic anemia. In all Cases, thiamine therapy did not resolve the clinical manifestation of deafness. In Cases 2 and 3, follow-up showed no blindness, unlike Case 4, in which treatment was started for megaloblastic anemia at age 7 but was increased to high doses only at age 25, when the genetic diagnosis of TRMA was performed. Conclusions: Early institution of high-dose thiamine supplementation seems to prevent the development of retinal changes and optic atrophy in TRMA patients. The spectrum of clinical manifestations is broad, and it is important to describe known Cases to gain a better understanding of this rare disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hainan Province is the southernmost island in China, far from the mainland, and the resident population changes little. In order to understand the mutation spectrum in Hainan and provide effective genetic counseling for deaf people, we carried out genetic analysis on the non-comprehensive hearing impairment in this population. Therefore, in this study, 183 children with moderate sensorineural deafness in the northeast of Hainan were analyzed with susceptibility gene carrying and gene mutation, providing some reference for hainan to guide the prevention and treatment of deafness. METHODS: Complete clinical evaluations were performed on 183 unrelated patients with a non-syndromic hearing impairment from Hainan Province. Each subject was screened for common mutations using the matrix-assisted laser desorption ionization-time of flight mass spectrometry, including GJB2 c.35d elG, c .235d elC,c .299_ 300de l AT,c. 176_1 91del 16,c. 167de lT; GJB3 c.538 C>T,c.547G >A;SLC26A4 IVS7-2 A>G,c.2168 A>G,c.1174A>T,c.1229 C>T,c .1226 G>A,c .1975 G>C,c .2027 T>A,c .2162 C>T,c .281C >T,c. 589G> A,IVS 15+5G >A; an d mtRNA 1494 C>T,1555 A>G. RESULTS: Genetic analysis showed that GJB2, SLC26A4, and mitochondrial M. 1555A > G mutations accounted for 7.10%, 8.74%, and 0.55% of the etiology of non-syndromic hearing impairment, respectively. Common mutations include GJB2 C. 235delC, SLC26A4 c.I vs7-2a →G, C. 2168A→G, and mitochondrial M. 1555A > G. The total mutation rate in Hainan was 16.39%. CONCLUSION: Our study is the first one to carry out genetic analysis on non-syndromic hearing impairment in Hainan. The results show that in the cases of non-syndromic hearing impairment in these areas, there is a clear genetic cause accounted for 16.39%, and the mutation hot spots are mainly GJB2 and SLC26A4, and SLC26A4 is the most common mutation site. This study provides useful and targeted information for genetic counseling of deafness in people with non-syndromic hearing impairment in Hainan. [ABSTRACT FROM AUTHOR]

We present these two cases to emphasize the necessity of critical thinking and high suspicion of the disease (Rogers syndrome) to avoid potentially fatal situations due to its rarity and the importance of early treatment. [ABSTRACT FROM AUTHOR]

Objective: Computed tomography (CT) images of the temporal bone of large vestibular aqueduct syndrome (LVAS) patients were used to establish 3D numerical models based on the structure of the inner ear, which are, in turn, used to construct inner ear fluid-solid coupling models. The physiological features and pathophysiology of LVAS were analyzed from a biomechanical perspective using finite element analysis.Methods: CT images of the temporal bone were collected from five children attending the Second Hospital of Dalian Medical University in 2022. The CT images were used to build 3D models of the inner ear containing the vestibular aqueduct (VA) by Mimics and Geomagic software, and round window membrane models and fluid-solid coupling models were built by ANSYS software to perform fluid-solid coupling analysis.Results: By applying different pressure loads, the deformation of the round window membranes occurred, and their trend was basically the same as that of the load. The deformation and stress of the round window membranes increased with the increase in load. Under the same load, the deformation and stress of the round window membranes increased with the expansion of the midpoint width of the VA.Conclusion: CT images of the temporal bone used clinically could establish a complete 3D numerical model of the inner ear containing VA. Fluctuations in cerebrospinal fluid pressure could affect inner ear pressure, and VA had a limiting effect on the pressure from cerebrospinal fluid. The larger the VA, the smaller the limiting effect on the pressure.

Abstract We present these two cases to emphasize the necessity of critical thinking and high suspicion of the disease (Rogers syndrome) to avoid potentially fatal situations due to its rarity and the importance of early treatment.

Type II diabetes mellitus (DMT II) is a major health threat, and DM is known to be associated with sensorineural deafness. Age, duration of DM, hypertension and hypertriglycerides are believed to influence this process. This study aims to determine the relationship between type II DM and the incidence of sensorineural hearing loss at Bali Royal General Hospital. The study used a case control design which was carried out on patients admitted between July-September 2021 at Bali Royal General Hospital. The sampling technique employed in the DMT II group with sensorineural deafness was total random sampling, while for comparison, simple random sampling was used. The analyses were carried out by descriptive analysis, chi square test for bivariate data, and logistic regression test for multivariate analysis. The p value is said to be meaningful if 0.05). The results of multivariate analysis found that there was no significant relationship between FBS levels and age with hearing conditions in the left ear (p> 0.05). In this study, there was no significant relationship between FBS, duration of DM, pattern of drug consumption, age, and hypertension status of DM patients with the incidence of SNHL in the right and left ears.

Bartter syndrome is a rare genetic disease with 5 subtypes. In Bartter syndrome type 4, patients suffer from deafness and renal dysfunction since infancy. In this report, we introduced a 16-year-old girl with congenital deafness without any previous renal complaints referred to our center due to ankle pain. [ABSTRACT FROM AUTHOR]

Background: HDR syndrome is a rare genetic disease caused by variants in the GATA3 gene and is phenotypically defined by the triad of hypoparathyroidism (H), deafness (D), and renal disease (R). Renal disorders of HDR are mainly developmental abnormalities, although renal functional abnormalities can also be observed. Nephrotic syndrome or nephrotic-level proteinuria is rare in HDR syndrome. Here, we report a Chinese infant with HDR syndrome who presented with early-onset nephrotic syndrome. We suggest that variants in the GATA3 gene might be associated with nephrotic syndrome., Case Summary: A 9-month-old boy was hospitalized with a complaint of diarrhea. Proteinuria was detected in the patient by routine testing for 3 days. No edema, oliguria, fever or abnormal urine color were observed. Routine urinary tests at a local hospital revealed proteinuria (protein 3 +) and microscopic hematuria (red blood cells 5-10/HP). The patient was born by cesarean delivery due to placental abruption at 35 weeks + 4 days of gestation. Intrauterine growth retardation was detected beginning at 6 months of gestation. His birth weight was 1.47 kg (< P3 th ), length was 39 cm (< P3 th ), and head circumference was 28 cm (< P3 th ). His motor developmental milestones were obviously delayed. Clinical data were analyzed, and genetic analysis for hereditary nephrotic syndrome was performed by next-generation sequencing. The clinical data showed that the boy exhibited growth retardation, early-onset nephrotic syndrome, microscopic hematuria, sensorineural deafness, T-cell immunodeficiency and congenital heart disease. Genetic tests revealed that the boy carried a de novo hemizygous variant, c.704C>T (p.Pro235 Leu), in exon 3 of the GATA3 gene., Conclusion: We report an infant with HDR syndrome who presented with early-onset nephrotic syndrome in China. We suggest that variants in the GATA3 gene might be associated with infant-onset nephrotic syndrome., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Abstract Introduction: Bartter’s syndrome comprises a heterogeneous group of inherited salt-losing tubulopathies. There are two forms of clinical presentation: classical and neonatal, the most severe type. Types I and II account for most of the neonatal cases. Types III and V are usually less severe. Characteristically Bartter’s syndrome type IV is a saltlosing nephropathy with mild to severe neonatal symptoms, with a specific feature - sensorineural deafness. Bartter’s syndrome type IV is the least common of all recessive types of the disease. Description: the first reported case of a Portuguese child with neurosensorial deafness, polyuria, polydipsia and failure to thrive, born prematurely due to severe polyhydramnios, with the G47R mutation in the BSND gene that causes Bartter’s syndrome type IV. Discussion: there are few published cases of BS type IV due to this mutation and those reported mostly have moderate clinical manifestations which begin later in life. The poor phenotype-genotype relationship combined with the rarity of this syndrome usually precludes an antenatal diagnosis. In the presence of a severe polyhydramnios case, with no fetal malformation detected, normal karyotype and after maternal disease exclusion, autosomal recessive diseases, including tubulopathies, should always be suspected.

Alström syndrome (ALMS) is an autosomal recessive disorder characterized by multiple organ involvement, including progressive cone-rod dystrophy, sensorineural hearing loss, childhood obesity, and type 2 diabetes mellitus. Pathogenic variants in the ALMS1 gene are the known cause for the occurrence of this devastating condition. Here we report on a 12 year old boy referred to the University Clinic with early signs of impaired hearing and vision, obesity, and scoliosis. Central vision was first affected, followed by peripheral vision. In addition, his weight began increasing after the age of two years, reaching 78 kg at a height of 157 cm (BMI 31.64). No polydactyly was present. His mental development was normal in spite of his hearing and vision impairments. There was acanthosis nigricans on the neck. ECG and the cardiac ultrasound were normal. At the age of 12 years, his testicles are 12 ml and his pubertal status is P2 A2. OGTT revealed impaired glucose tolerance with elevated insulin concentrations 121ulU/mL (reference range 2,00-29,1 ulU/mL). Renal function was unaffected, liver functions were normal. Uric acid and lipids were within normal plasma concentrations. A Whole Exome Sequencing was performed and a homozygous ALMS1 pathogenic, frameshift gene variant (LRG_741t1(ALMS1):c.4156dup; p.Thr1386AsnfsTer15) was determined as the cause of the disease. Both parents were carriers for the variant. The absence of mental retardation and polydactyly differentiates Alström and Bardet-Biedle syndrome. [ABSTRACT FROM AUTHOR]

A middle-aged homemaker, known sickle cell anaemia patient presented with complaints of reduced vision and night blindness since childhood along with recent-onset hearing impairment in both ears. Anterior segment findings revealed lens opacities more in the left eye, whereas fundus findings showed widespread bone spicule pigmentation in both eyes. Pure-tone audiometry indicated bilateral sensorineural hearing loss. With improvement in visual acuity after refraction, the corrective spectacle was prescribed along with a hearing aid. She presently maintains a follow-up appointment with the sickle cell, ophthalmology, and ear, nose, and throat clinics for a routine checkup. She has improved in her general health and has been crisis-free since the presentation.

Objective:Bi-allelic mutations in the wolframin gene (WFS1) cause Wolfram syndrome 1 (WS1 or DIDMOAD) characterized by non-autoimmune diabetes mellitus, optic atrophy, diabetes insipidus, sensorineural deafness, urinary tract abnormalities, and neuropsychiatric disorders. Patients presenting with an incomplete phenotype of WS1 were evaluated using homozygosity mapping and subsequent whole-exome sequencing.Methods:Four unrelated consanguineous Turkish families, including seven affected children, and their unaffected parents and siblings were evaluated. Homozygosity mapping was performed, followed by whole-exome sequencing of WFS1. Mutations were classified according to results of “in silico” analyses, protein prediction, and functional consequences.Results:Homozygosity mapping confirmed shared homozygous regions on chromosome 4 (chr4p16.1) between the affected individuals, that was absent in their unaffected siblings. Exome sequencing identified three novel (c.1215T>A, c.554G>A, c.1525_1540dup) and one known (c.1522_1523delTA) mutations in WFS1. All mutations were predicted to cause stop codon leading to early termination of protein synthesis and complete loss-of-function. All patients were found to be homozygous for the change, with parents and other unaffected siblings being carriers.Conclusion:Our study expands the mutation spectrum of WSF1 mutations with three novel mutations. Homozygosity mapping may provide enrichment for molecular genetic analysis and early diagnosis of WS1 patients with incomplete phenotype, particularly in consanguineous pedigrees.

Topicality: The research conducted by the authors shows that acute trauma in combat conditions is accompanied by persistent psychophysiological disorders of the central nervous system, but a significant part of these studies is based on clinical observation data. The technique of electroencephalography (EEG) allows you to objectively assess the state of the central nervous system and provides a better understanding of neurophysiological processes in patients with sensorineural deafness (SND) with acute trauma, which will contribute to the development of more effective rehabilitation methods for this contingent of patients. Aim: to evaluate the indicators of bioelectrical activity of the brain according to electroencephalography (EEG) data in servicemen who received acute trauma in real combat conditions, with different effectiveness of treatment measures. Materials and methods: 2 groups of servicemen with combat acute trauma were examined: 1 group - patients with positive dynamics of treatment, 2 group - patients with insufficient effectiveness of treatment, and 15 healthy normal-sensing individuals of the control group. The electroencephalographs study was carried out with the help of a computer electroencephalograph of the company "DH-systems" (Ukraine). Results: All patients underwent a comprehensive, instrumental examination. The examined subjects had sensorineural deafness with a descending, often abrupt, type of tonal audiometric curve, with the most pronounced and reliable increase in hearing sensitivity thresholds in the region of 4, 6, and 8 kHz. According to the analysis of EEG indicators, in the patients examined by us, the most characteristic were a decrease in the bioelectric activity of the brain and disorganization of cortical rhythms with signs of dysfunction of the diencephalon-stem structures. At the same time, the decrease in bioelectric activity most often occurred in the frontal and temporal leads. Thus, in patients of group 1, during the background recording, the content of the delta rhythm was (13,61±0,37) and (9,96±0,29) %, respectively, which significantly exceeds the control indicators (8,5±1,6) and (5,3±1,5) % (Р<0,05). During photostimulation and hyperventilation in the frontal leads, the content of slow-wave activity significantly exceeded the control indicators. During photostimulation, the content of the delta rhythm in patients of group 1 was (14,23±0,38) and (7,3±1,4) % in the control group. In the comparative analysis of EEG indicators between the studied groups, an increase in the representation of slow-wave activity in frontal projections and a decrease in the share of alpha rhythm in patients of group 2 is noted. Thus, in frontal leads during background recording in patients of groups 1 and 2, the delta rhythm content was (13,61±0,37) and (16,95±0,25) %, respectively. Moreover, these trends were preserved both during background recording and during functional loads. Therefore, patients with combat acute trauma have significant disturbances in the bioelectrical activity of the brain according to EEG data. Patients with pronounced disorders of the functional state of the central nervous system are more difficult to treat with SNP. Conclusions: 1. Military personnel with acute trauma received in real combat conditions have objective signs of functional disorders in the cortical and deep structures of the brain according to EEG data. 2. Prognostically unfavourable in terms of treatment effectiveness is the redistribution of the main EEG rhythms in the direction of growth of slow-wave activity on a disorganized background, especially in frontal projections. It is advisable to take this into account when carrying out treatment and preventive measures and developing rehabilitation measures. 3. Targeted treatment of sensorineural deafness in patients with combat acute trauma should be carried out taking into account extraural disorders, which allows to prevent the development of severe deafness. [ABSTRACT FROM AUTHOR]

Objective: to identify the frequency and type of ocular problems in pediatric patients with sensorineural deafness, in a national reference center for hearing problems in Guatemala. Material and methods: cross-sectional and prospective study carried out in 24 patients younger than 14 years with sensorineural hearing loss. All patients underwent a complete ophthalmologic examination. Results: age ranged from two to 13 years, and most were male (n = 17, 70.8%). Of the total, 15 patients (62.5%) presented ocular problems; of which, 11 patients presented refractive defects, six strabismus, and six minor findings in the anterior segment and in ocular adnexa. Conclusion: children with sensorineural deafness have ocular problems that require identification and treatment, so it is recommended to perform an ophthalmological evaluation as soon as possible. [ABSTRACT FROM AUTHOR]

Abstract Autosomal dominant hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome are typically diagnosed by manifestations of the three features with a positive family history. Our case carried a de novo variant in causative gene, GATA3, but presenting no renal dysplasia or family history. The phenotypic heterogeneity raises a caution for diagnosis.

The article explores how is a patient suspected to have hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome diagnosed. Topics include the diagnosis of HDR syndrome is based on the manifestation of hypoparathyroidism, deafness, and kidney dysplasia; and transplantation would reduce the frequency of recurrent pancreatitis in our case by reducing the uremic toxins.

Retinitis Pigmentosa (RP) is a genetically heterogeneous group of inherited retinal disorders causing progressive dysfunction of rod photoreceptor and retinal pigment epithelium, may be seen in isolation or in association with systemic disease. This paper focuses on RP in an atypical type IV usher’s patient. Usher’s syndrome is a rare disorder and is the most common hereditary form of deaf-blindness. The management of these patients is multidisciplinary, involving specialists from different fields. Hereby, author present a case of 47-year-old male patient presented with chief complaints of defective vision in both eyes and defective vision in dim light for past six months. On fundus examination of both the eyes, he was diagnosed to have bilateral RP and on pure tone audiometry, he was diagnosed to have bilateral sensorineural deafness. Molecular gene analysis was done and it revealed Arylsulfatase G (ARSG) gene mutation. The patient was prescribed spectacles for his visual improvement.

Wolff-Parkinson-White (WPW) syndrome is a condition associated with tachycardia due to accessory pathways in the heart, and it is one of the most common causes of tachycardia in infants and children. WPW may also be associated with mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS syndrome) or LEOPARD syndrome (LS). We report a case of pre-excitation WPW syndrome in a 17-year-old man who was brought to the hospital by ambulance following the collapse. WPW syndrome type A was diagnosed from precordial leads. Electrocardiography (ECG) revealed a short PR interval, delta waves, and positive waves with dominant R in all pericardial leads. Blood test results showed an isolated elevated ALT level. Subsequent echocardiography was unremarkable, with an ejection fraction of 55%, apart from septal and inferior wall dyssynchrony. With regard to the past medical history, he had sensorineural deafness (SND) since childhood and had a family history of SND. Consequently, the patient was transferred to the cardiac electrophysiology department at another hospital after consultation and underwent ablation. A successful post-ablation electrocardiogram revealed the resolution of the WPW syndrome signs and post-ablation features, such as peak T waves., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Khan et al.)

Mutations in nuclear genes regulating mitochondrial DNA (mtDNA) replication are associated with mtDNA depletion syndromes. Using whole-genome sequencing, we identified a heterozygous mutation (c.272G>A:p.Arg91Gln) in single-stranded DNA-binding protein 1 (SSBP1), a crucial protein involved in mtDNA replisome. The proband manifested symptoms including sensorineural deafness, congenital cataract, optic atrophy, macular dystrophy, and myopathy. This mutation impeded multimer formation and DNA-binding affinity, leading to reduced efficiency of mtDNA replication, altered mitochondria dynamics, and compromised mitochondrial function. To correct this mutation, we tested two adenine base editor (ABE) variants on patient-derived fibroblasts. One variant, NG-Cas9-based ABE8e (NG-ABE8e), showed higher editing efficacy (≤30%) and enhanced mitochondrial replication and function, despite off-target editing frequencies; however, risks from bystander editing were limited due to silent mutations and off-target sites in non-translated regions. The other variant, NG-Cas9-based ABE8eWQ (NG-ABE8eWQ), had a safer therapeutic profile with very few off-target effects, but this came at the cost of lower editing efficacy (≤10% editing). Despite this, NG-ABE8eWQ-edited cells still restored replication and improved mtDNA copy number, which in turn recovery of compromised mitochondrial function. Taken together, base editing-based gene therapies may be a promising treatment for mitochondrial diseases, including those associated with SSBP1 mutations., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Athabaskan Brainstem Dysgenesis Syndrome (ABDS) is a nonlethal, homozygous HOXA1 mutation typically marked by central hypoventilation, sensorineural deafness, horizontal gaze palsy, and developmental delay. In this report, we present a case of a 27-month-old Navajo female with a new diagnosis of ABDS after multiple failed attempts at extubation following anesthesia in the setting of respiratory syncytial virus (RSV) bronchiolitis. Her case is significant because she lacks sensorineural hearing loss, a defining feature of previously documented cases thereby underscoring the challenges of diagnosing this disease. This case expands the ever-growing spectrum of homozygous HOXA1 mutations and demonstrates unique junctions for diagnosis of ABDS in the critical care setting in patients lacking key features of the disease.

Syndrome of (hypoparathyroidism, deafness and renal disease) HDS is a rare autosomal dominant syndrome which is characterized by triad of hypoparathyroidism, sensorineural hearing loss and renal disease. The syndrome is caused by mutation of GATA3 gene on chromosome 10p. We report a case of 7 years old boy who presented in Bahawalpur Victoria Hospital Bahawalpur, Pakistan with recurrent tetanic spells, muscular aches and pains for last 15 days. He was operated four years back for renal stones. His blood complete picture was normal except for mild anemia. His serum calcium level was low i.e. 6.9 mg/dL. Serum magnesium, phosphate, alkaline phospha-tase and Vitamin D levels were normal. Serum PTH (parathyroid hormone) level was low i.e. 4.51 pg/ml (Normal range 11-67 pg/mL). Urine RE showed albumin, pus cells and calcium oxalate crystals. Pure tone audiometry showed bilateral mild to moderate degree of sensorineural hearing loss.

They found that the p38 signaling pathway plays a vital role in I dusp14 i knockdown-related hearing defects, and p38 inhibitor treatment could reverse I dusp14 i knockdown-induced absence of supporting cells and proliferation disability. Together, the achievements included in this Research Topic contribute to further understanding of the pathogenesis of hearing loss, attracting the interest of readers in hearing-related research, and providing a reference for the development of novel hearing loss therapies. Keywords: sensorineural deafness; hearing loss; hair cell; neuron; auditory organ EN sensorineural deafness hearing loss hair cell neuron auditory organ 1 3 3 06/14/22 20220610 NES 220610 Damage to the auditory system is associated with many factors, including genetic deficiency, aging, ototoxic drugs, noise, infection, and many other environmental factors. [Extracted from the article]

Abstract Background Progressive bilateral sensorineural deafness in postlingual period may be linked to many different etiologies including genetic factors. Identification of the exact deafness cause may, therefore, be quite challenging. Here we present a family with late-onset hearing loss as an autosomal dominant trait caused by a novel EYA4 mutation. Case presentation Forty-four years old female proband clinically investigated for progressive hearing loss and occasional dizziness with positive family history for deafness was subject to molecular-genetic testing. Patient’s DNA sample was analyzed by whole exome sequencing. We identified a novel missense variant c.804G > C located at the last base pair of exon 10 in EYA4. Candidate variant was confirmed by Sanger sequencing in the proband and her family members. In silico prediction tools and co-segregation analysis were used to indicate pathogenicity of the identified variant. To confirm our hypothesis, we performed minigene assay to demonstrate if the transcript of exon 10 in EYA4 is present. We provide evidence that this mutation in vitro compromises donor site functionality and causes exon 10 skipping and frameshift that most likely results in nonsense-mediated mRNA decay. The onset of moderate to severe hearing loss in the family ranged from 10 to 40 years. The normal cardiac phenotype was confirmed by ECG and echocardiography. Conclusions We identified a novel EYA4 mutation associated with adult-onset autosomal dominant sensorineural hearing loss. This report extends the knowledge of spectrum of EYA4 mutations and demonstrates the pathogenicity of a variant affecting specific position in the gene. A comprehensive review of known EYA4 mutations is also given and their impact on cardiac phenotype is discussed. Our findings highlight the importance of genetic testing and complex clinical assessment in patients with familial progressive hearing loss.

Astrocytic hamartomas are benigh tumors that arise in retina and / or optic nerve anterior to lamina cribrosa (optic nerve head). Hamartomas can be solitary or may be associated with phakomatosis. A 15 year-old patient presented with complaint of night blindness since childhood. Ocular examination showed pigmentary retinopathy at mid peripheral retina with superficial globules at optic nerve head margin in both eyes. Multimodal imaging was done to diagnose it as astrocytic hamartoma. Systemic examination revealed profound sensorineural hearing loss. Family history was positive for retinitis pigmentosa. This case report describes the rare association of astrocytic hamartomas with retinitis pigmentosa..

Reversible splenial lesion syndrome (RESLES) is a rare clinico-radiological disorder syndrome with unclear pathophysiology. Here, two sisters with sensorineural deafness as the chief complaint diagnosed with RESLES was reported. Although the sisters had the disease successively, they were divided into two types on imaging by isolated lesions of splenium of the corpus callosum (SCC) and extensive lesions of the corpus callosum. The clinical manifestations and lesions on MRI disappeared after 6 months. The sensorineural deafness of the sisters in this article may be caused by transcallosal auditory pathway (TCAP) injury. Auditory handicap has been found in previous RESLES cases, indicating that we know little about the connection between the SCC and the auditory pathway, and further research is needed.

Congenital cranial dysinnervation disorders (CCDDs) are a heterogeneous group of neurodevelopmental phenotypes caused by a primary disturbance of innervation due to deficient, absent, or misguided cranial nerves. Although some CCDDs genes are known, several clinical phenotypes and their aetiologies remain to be elucidated. We describe a 12‐year‐old boy with hypotonia, developmental delay, sensorineural hearing loss, and keratoconjunctivitis due to lack of corneal reflex. He had a long expressionless face, severe oromotor dysfunction, bilateral agenesis/severe hypoplasia of the VIII nerve with marked atresia of the internal auditory canals and cochlear labyrinth malformation. Trio‐exome sequencing identified a homozygous loss of function variant in the NEUROG1 gene (NM_006161.2: c.202G > T, p.Glu68*). NEUROG1 is considered a causal candidate for CCDDs based on (i) the previous report of a patient with a homozygous gene deletion and developmental delay, deafness due to absent bilateral VIII nerves, and severe oromotor dysfunction; (ii) a second patient with a homozygous NEUROG1 missense variant and corneal opacity, absent corneal reflex and intellectual disability; and (iii) the knockout mouse model phenotype which highly resembles the disorder observed in humans. Our findings support the growing compelling evidence that loss of NEUROG1 leads to a very distinctive disorder of cranial nerves development. [ABSTRACT FROM AUTHOR]

Introduction: Bartter's syndrome comprises a heterogeneous group of inherited salt-losing tubulopathies. There are two forms of clinical presentation: classical and neonatal, the most severe type. Types I and II account for most of the neonatal cases. Types III and V are usually less severe. Characteristically Bartter's syndrome type IV is a saltlosing nephropathy with mild to severe neonatal symptoms, with a specific feature - sensorineural deafness. Bartter's syndrome type IV is the least common of all recessive types of the disease. Description: the first reported case of a Portuguese child with neurosensorial deafness, polyuria, polydipsia and failure to thrive, born prematurely due to severe polyhydramnios, with the G47R mutation in the BSND gene that causes Bartter's syndrome type IV. Discussion: there are few published cases of BS type IV due to this mutation and those reported mostly have moderate clinical manifestations which begin later in life. The poor phenotype-genotype relationship combined with the rarity of this syndrome usually precludes an antenatal diagnosis. In the presence of a severe polyhydramnios case, with no fetal malformation detected, normal karyotype and after maternal disease exclusion, autosomal recessive diseases, including tubulopathies, should always be suspected. [ABSTRACT FROM AUTHOR]

Objective: Bi-allelic mutations in the wolframin gene (WFS1) cause Wolfram syndrome 1 (WS1 or DIDMOAD) characterized by nonautoimmune diabetes mellitus, optic atrophy, diabetes insipidus, sensorineural deafness, urinary tract abnormalities, and neuropsychiatric disorders. Patients presenting with an incomplete phenotype of WS1 were evaluated using homozygosity mapping and subsequent whole-exome sequencing. Methods: Four unrelated consanguineous Turkish families, including seven affected children, and their unaffected parents and siblings were evaluated. Homozygosity mapping was performed, followed by whole-exome sequencing of WFS1. Mutations were classified according to results of "in silico" analyses, protein prediction, and functional consequences. Results: Homozygosity mapping confirmed shared homozygous regions on chromosome 4 (chr4p16.1) between the affected individuals, that was absent in their unaffected siblings. Exome sequencing identified three novel (c.1215T>A, c.554G>A, c.1525_1540dup) and one known (c.1522_1523delTA) mutations in WFS1. All mutations were predicted to cause stop codon leading to early termination of protein synthesis and complete loss-of-function. All patients were found to be homozygous for the change, with parents and other unaffected siblings being carriers. Conclusion: Our study expands the mutation spectrum of WSF1 mutations with three novel mutations. Homozygosity mapping may provide enrichment for molecular genetic analysis and early diagnosis of WS1 patients with incomplete phenotype, particularly in consanguineous pedigrees. [ABSTRACT FROM AUTHOR]

Introduction: The world community is concerned with the assessment of the speech and hearing development of children with sensorineural deafness after cochlear implantation, since the most important result of rehabilitation is the success of social integration of such children. In most countries of the world, the Meaningful Auditory Integration Scale (MAIS) and the Meaningful Use of Language Scale (MUSS) are used to assess the auditory and language integration of children with sensorineural hearing loss after cochlear implantation (CI). Unfortunately, in Ukraine there are still no Ukrainian questionnaires for assessing the auditory development of children with sensorineural hearing loss after cochlear implantation. The aim of our study was to translate MAIS and MUSS manuals into Ukrainian, to adapt and validate them culturally. Materials and methods: Materials for translation and cultural adaptation were English-language versions of the Meaningful Auditory Integration Scale (MAIS) and Meaningful Use of Language Scale (MUSS), developed by the Nottingham Group of Cochlear Implantation, which are recognized and recommended for use by all cochlear implant manufacturers. Results obtained: The evaluation consisted of the following stages: preparatory stage - collection and analysis of literature; translation of original texts from English into Ukrainian; reversed translation by an independent translator of Ukrainian text into English; collation of the translation and comparison with the original questionnaire by an independent linguist; Cognitive analysis; field-testing of textbooks translated into Ukrainian with a small group of children after the CI; corrections, final revision of translations to identify and correct any grammatical, orthographic and other errors. The Ukrainian version of the questionnaire demonstrated a high level of internal compliance, testability and validity. Conclusions: Given the considerable relevance and demand ability of the materials, the tests can be recognized as valid and recommended for use in cochlear implant rehabilitation process. [ABSTRACT FROM AUTHOR]

IntroductionKallmann syndrome (KS) is idiopathic hypogonadotropic hypogonadism with olfactory loss or decline. Waardenburg syndrome type II (WS2) is a clinically and genetically heterogeneous disease, characterized by congenital sensorineural deafness and abnormal pigmentation of the iris, hair, and skin. Recently, mutations in the well-known WS pathogenic gene SOX10 have been found in some KS patients with deafness, but whether SOX10 is a co-pathogenic gene of KS and WS remains uncertain. Here, we report a rare case of KS and WS2 co-occurrence due to SOX10 mutations.MethodsDetailed histories were collected through questionnaires and physical examination. Blood samples of the patient and his family members were collected after obtaining informed consents. Suspected mutations were amplified and verified by Sanger sequencing after the next generation sequencing of related genes. The raw sequence data were compared to the known gene sequence data in publicly available sequence data bases using Burrows-Wheeler Aligner software (BWA, 0.7.12-r1039).ResultsA 28-year-old male patient sought treatment for hypogonadism and the absence of secondary sexual characteristics. In addition, he showed signs of obesity, hyposmia, sensorineural hearing loss, and blue iris. Magnetic resonance imaging (MRI) of the olfactory bulb showed small bilateral olfactory bulbs and tracts and diaphragma cerebri. MRI of the pituitary gland revealed a flat pituitary gland in the sella. Laboratory examination demonstrated hypogonadotropic hypogonadism, pituitary hypothyroidism, subclinical hypothyroidism, and the presence of insulin resistance with normal blood glucose levels. Sequencing of the SOX10 gene showed a 20 bp insertion in between coding bases 1,179 and 1,180 (c.1179_1180insACTATGGCTCAGCCTTCCCC). This results in a frame-shifting mutation of the 394th amino acid serine in exon4 with the resulting the amino acid sequence of the protein predicted to be TMAQPSP PSPAPSLTTL TISPQDPIMA TRARPLASTR PSPIWGPRSG PSTRPSLTPA PQGPSPTAPH TGSSQYIRHC PGPKGGPVAT TPRPAPAPSL CALFLAHLRP GGGSGGG*.ConclusionSOX10 plays an important role in some critical stages of neural crest cell development and SOX10 mutation may be a common pathogenic factor for both KS and WS. Therefore, SOX10 mutation analysis should be considered for KS patients with combined WS clinical manifestations, especially deafness.

Introduction: Kallmann syndrome (KS) is idiopathic hypogonadotropic hypogonadism with olfactory loss or decline. Waardenburg syndrome type II (WS2) is a clinically and genetically heterogeneous disease, characterized by congenital sensorineural deafness and abnormal pigmentation of the iris, hair, and skin. Recently, mutations in the well-known WS pathogenic gene SOX10 have been found in some KS patients with deafness, but whether SOX10 is a co-pathogenic gene of KS and WS remains uncertain. Here, we report a rare case of KS and WS2 co-occurrence due to SOX10 mutations. Methods: Detailed histories were collected through questionnaires and physical examination. Blood samples of the patient and his family members were collected after obtaining informed consents. Suspected mutations were amplified and verified by Sanger sequencing after the next generation sequencing of related genes. The raw sequence data were compared to the known gene sequence data in publicly available sequence data bases using Burrows-Wheeler Aligner software (BWA, 0.7.12-r1039). Results: A 28-year-old male patient sought treatment for hypogonadism and the absence of secondary sexual characteristics. In addition, he showed signs of obesity, hyposmia, sensorineural hearing loss, and blue iris. Magnetic resonance imaging (MRI) of the olfactory bulb showed small bilateral olfactory bulbs and tracts and diaphragma cerebri. MRI of the pituitary gland revealed a flat pituitary gland in the sella. Laboratory examination demonstrated hypogonadotropic hypogonadism, pituitary hypothyroidism, subclinical hypothyroidism, and the presence of insulin resistance with normal blood glucose levels. Sequencing of the SOX10 gene showed a 20 bp insertion in between coding bases 1,179 and 1,180 (c.1179_1180insACTATGGCTCAGCCTTCCCC). This results in a frame-shifting mutation of the 394th amino acid serine in exon4 with the resulting the amino acid sequence of the protein predicted to be TMAQPSP PSPAPSLTTL TISPQDPIMA TRARPLASTR PSPIWGPRSG PSTRPSLTPA PQGPSPTAPH TGSSQYIRHC PGPKGGPVAT TPRPAPAPSL CALFLAHLRP GGGSGGG*. Conclusion: SOX10 plays an important role in some critical stages of neural crest cell development and SOX10 mutation may be a common pathogenic factor for both KS and WS. Therefore, SOX10 mutation analysis should be considered for KS patients with combined WS clinical manifestations, especially deafness. [ABSTRACT FROM AUTHOR]

Among the electroneutral Na+-dependent chloride transporters, NKCC1 had until now evaded identification as a protein causing human diseases. The closely related SLC12A transporters, NKCC2 and NCC have been identified some 25 years ago as responsible for Bartter and Gitelman syndromes: two renal-dependent salt wasting disorders. Absence of disease was most surprising since the NKCC1 knockout mouse was shown in 1999 to be viable, albeit with a wide range of deleterious phenotypes. Here we summarize the work of the past 5 years that introduced us to clinical cases involving NKCC1. The most striking cases are of 3 children with inherited mutations, who have complete absence of NKCC1 expression. These cases establish that lack of NKCC1 causes deafness; CFTR-like secretory defects with mucus accumulation in lung and intestine; severe xerostomia, hypotonia, dysmorphic facial features, and severe neurodevelopmental disorder. Another intriguing case is of a patient with a dominant deleterious SLC12A2 allele. This de novo mutation introduced a premature stop codon leading to a truncated protein. This mutant transporter seems to exert dominant-negative effect on wild-type transporter only in epithelial cells. The patient who suffers from lung, bladder, intestine, pancreas, and multiple endocrine abnormalities has, however, normal hearing and cognition. Finally, new reports substantiate the haploinsufficiency prediction of the SLC12A2 gene. Cases with single allele mutations in SLC12A2 have been linked to hearing loss and neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Autosomal dominant hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome are typically diagnosed by manifestations of the three features with a positive family history. Our case carried a de novo variant in causative gene, GATA3, but presenting no renal dysplasia or family history. The phenotypic heterogeneity raises a caution for diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Background Barakat syndrome is an autosomal dominant disorder characterized by the triad of hypoparathyroidism, sensorineural deafness, and renal anomalies and is caused by mutations in GATA3 gene. SLC34A3 is the cause gene of hypophosphatemic rickets with hypercalciuria, and heterozygous carriers may have milder clinical symptoms. The aim of this study was to identify the underlying genetic cause of a patient who initially presented with renal failure, hypercalciuria, kidney stone, and bilateral sensorineural deafness. Methods A 6‐year‐old boy with complex clinical presentations was investigated. Comprehensive medical evaluations were performed including auditory function tests, endocrine function tests, metabolic studies, and imaging examinations. Molecular diagnoses were analyzed by trio whole‐exome sequencing. Results One novel de novo deleterious variant (c. 324del) of the GATA3 gene was identified in the patient. The patient can be diagnosed with Barakat syndrome. In addition, one novel variant (c. 589A>G) of the SLC34A3 gene was detected, which was inherited from the father. This heterozygous variant can explain the hypercalciuria and kidney stone that occurred in both the patient and his father. Conclusion This study provides a special case which is phenotype‐driven dual diagnoses, and the two novel variants can parsimoniously explain the complex clinical presentations of this patient.

Retinitis Pigmentosa (RP) is a genetically heterogeneous group of inherited retinal disorders causing progressive dysfunction of rod photoreceptor and retinal pigment epithelium, may be seen in isolation or in association with systemic disease. This paper focuses on RP in an atypical type 4 usher's patient. Usher's syndrome is a rare disorder and is the most common hereditary form of deafblindness. The management of these patients is multidisciplinary, involving specialists from different fields. Hereby, author present a case of 47-year-old male patient presented with chief complaints of defective vision in both eyes and defective vision in dim light for past six months. On fundus examination of both the eyes, he was diagnosed to have bilateral RP and on pure tone audiometry, he was diagnosed to have bilateral sensorineural deafness. Molecular gene analysis was done and it revealed Arylsulfatase G (ARSG) gene mutation. The patient was prescribed spectacles for his visual improvement. [ABSTRACT FROM AUTHOR]

A case study of a patient was delivered at 36 weeks and 3 days of pregnancy via cesarean section, and a case of hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome with kidney failure and recurrent pancreatitis. Topics include patient's parathyroid hormone and serum calcium levels were low during the neonatal period; and patient had been diagnosed with iron deficiency anemia of an unknown origin in the neonatal period, he had been administered ferric pyrophosphate.

Background: A number of inborn errors of metabolism caused by abnormal protein trafficking that lead to endoplasmic reticulum storage diseases (ERSD) have been defined in the last two decades. One such disorder involves biallelic mutations in the gene encoding endoplasmic reticulum resident co‐chaperone DNAJC3 (P58IPK) that leads to diabetes in the second decade of life, in addition to multiple endocrine dysfunction and nervous system involvement. Objective: The aim of this study was to define the natural history of this new form of diabetes, especially the course of abnormalities related to glucose metabolism. Methods: Whole‐exome and Sanger sequencing was used to detect DNAJC3 defect in two patients. Detailed analysis of their clinical history as well as biochemical, neurological and radiological studies were carried out to deduce natural history of neurological and endocrine phenotype. Results: DNAJC3 defect led to beta‐cell dysfunction causing hyperinsulinemichypoglycemia around 2 years of age in both patients, which evolved into diabetes with insulin deficiency in the second decade of life, probably due to beta cell loss. Endocrine phenotype involved severe early‐onset growth failure due to growth hormone deficiency, and hypothyroidism of central origin. Neurological phenotype involved early onset sensorineural deafness discovered around 5 to 6 years, and neurodegeneration of central and peripheral nervous system in the first two decades of life. Conclusion: Biallelic loss‐of‐function in the ER co‐chaperone DNAJC3 leads to a new form of diabetes with early onset hyperinsulinemic hypoglycemia evolving into insulin deficiency as well as severe growth failure, hypothyroidism and diffuse neurodegeneration. [ABSTRACT FROM AUTHOR]