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Primary renal hypouricemia (RHUC) is a rare autosomal recessive disorder with a mean duration of end-stage acute kidney injury (EIAKI) of 14 days. The pathogenesis of EIAKI in patients with RHUC remains unclear. Several hypotheses have been proposed, including those related to the renal vasoconvulsive effect and the elevating effect of xanthine oxidase (XO). The effect of xanthine oxidase (XO) is most often observed following strenuous anaerobic exercise, which is frequently accompanied by low back pain, nausea, and acute kidney injury (AKI). Consequently, we postulate that EIAKI could be prevented by avoiding strenuous exercise, thus preventing the onset and recurrence of EIAKI. In this paper, we present a case of recurrent EIAKI in a patient with RHUC and a mutation in the SLC2A9 gene. [ABSTRACT FROM AUTHOR]

Background/Objectives: Biallelic mutations in the PTRH2 gene are associated with a rare genetic disease known as infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). In this study, we describe a new case carrying a previously identified mutation, provide an updated analysis of the relative frequencies of the clinical features across all published cases (including the three latest studies), and perform a bioinformatics analysis of the newly identified PTRH2 protein variants from a structural perspective. Methods: Clinical examination of the patients was carried out, and genetic testing was performed using a genome sequencing strategy. A bioinformatics analysis was carried out for the newly reported mutations using PYMOL that was utilized to view the structure and analyze the mutations. Additionally, the ThermoMPNN webserver was employed to check the effect of point mutations on the overall stability of the protein. Results: Our findings indicate that motor delay, neuropathy, intellectual disability, distal weakness, hearing impairment, and ataxia are the most common symptoms, while the other clinical features fall into two frequency categories: moderately common ones and the least common ones. The bioinformatics analysis revealed that the Q85 residue is highly conserved, suggesting that mutations at this position could disrupt key signaling pathways or cellular functions. Indeed, the Q85R mutation was shown to significantly impair the stability and functionality of the protein. Conclusions: The clinical presentation of IMNEPD remains highly variable in terms of both severity and progression. Mutations at the Q85 residue have been identified in nearly 50% of reported cases, highlighting this position as a potential mutational hotspot in the PTRH2 protein. [ABSTRACT FROM AUTHOR]

Background: Targeted next generation sequence analyses in a cohort of 961 previously described patients with clinically suspected Duchene muscular dystrophy (DMD) revealed that 145/961 (15%) had variants in genes associated with other muscular dystrophies (OMDs). Methods: NGS was carried out in DMD negative patients after deletion/duplication analysis followed by WES for No variant cases. Results: The majority of patients with OMDs had autosomal recessive diseases that included Limb‐Girdle Muscular Dystrophies (LGMDs), Bethlem, Ullrich congenital Myopathies and Emery‐Driefuss muscular dystrophy. 3.5% of patients were identified with other disorders like Charcot‐Marie Tooth and Nemaline myopathy. A small percentage of patients, 0.6% remain undiagnosed. Of a total of 78 genetic variants identified, 44 were found to be novel. Interestingly, a third of patients with OMDs were found to have LGMD2E/R4, a severe form of LGMD that afflicts young children with clinical symptoms similar to DMD. Almost one third of the unrelated LGMD2E/R4 patients had the same point mutation (c.544A>C) in the SGCB gene, suggestive of a founder effect, described here for the first time in India. Conclusion: This study underscores the need for a complete genetic work up to precisely diagnose patients and to initiate appropriate counseling programs, disease management and prevention strategies. [ABSTRACT FROM AUTHOR]

Limb-girdle muscular dystrophy type 2A (LGMD R1 Calpain 3-Related, LGMD2A/R1), an autosomal recessive disorder, is characterized by progressive muscle weakness with a prominent presentation in the proximal limb girdle muscles. LGMD2A/R1, which is caused by variants in calcium-activated neutral proteinase 3 (CAPN3), is the most common. The present study aimed at identifying the clinically significant variants in a Chinese family with LGMD2A/R1 and exploring the genotype-phenotype correlations. Clinical symptoms, laboratory findings, and physical examinations were obtained. Genomic DNA was extracted from the peripheral blood samples of this family. Whole-exome sequencing (WES) and Sanger sequencing were used to explore and validate the pathogenic genes. In this study, the proband and his sister, who had two identical mutations in the CAPN3 gene sequence, exhibited diverse clinical features, including disease onset and progression. The mutation c.2120 A>G (p. D707G) is pathogenic and has been reported in the Human Gene Mutation Database (HGMD) and the ClinVar database. c.1783-72 C>G may be a novel pathogenic mutation of LGMD2A/R1 based on the American College of Medical Genetics (ACMG) guidelines, which widens the gene variant pool in CAPN3 and improves diagnosis and genetic counseling. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is an autosomal recessive disorder altering the shape of red blood cells, causing harmful obstructions in blood vessels, therefore altering normal blood flow. SCD can escalate quickly into acute chest syndrome (ACS), a life-threatening complication that requires immediate care. This article discusses the pathophysiology, assessment, diagnosis, and treatment of ACS, as well as nursing care and patient education. [ABSTRACT FROM AUTHOR]

Nijmegen syndrome is a primary immunodeficiency characterized by chromosomal instability, microcephaly, physical retardation, specific disorders of the facial skeleton, as well as a predisposition to cancer. Most patients of Slavic origin have a homozygous mutation with the del5 founder effect in the NBS gene. The frequency of occurrence is 1:100000population. The highest frequency of carriage in the population of the del5 mutation in the NBS gene in the Czech Republic is 1:154, in Ukraine – 1:182, in Poland – 1:190. This pathology is presented in our clinical practice for the first time, and therefore we would like to provide data for a wide review

Glanzmann thrombasthenia and clotting factor VII deficiency are rare autosomal recessive bleeding disorders. But the occurrence of both in the same person is an extremely rare phenomenon. Here, we present the case of a young female from Sindh, Pakistan that got diagnosed with Glanzmann thrombasthenia and concomitant moderate factor VII deficiency, a combination not previously reported in the country. The patient exhibited typical clinical manifestations including menorrhagia, nasal bleeds, and prolonged bleeding after minor injuries, compounded by a positive family history and consanguinity. Laboratory investigations revealed marked anemia, prolonged bleeding time, and abnormal platelet aggregation studies consistent with Glanzmann thrombasthenia. The identification of this rare combination relied on comprehensive clinical evaluation, emphasizing the importance of family history in suspected cases. Management involved platelet transfusions, tranexamic acid, and Factor VII replacement, resulting in clinical improvement. [ABSTRACT FROM AUTHOR]

Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive disorders that occur due to defects in steroid synthesis. It is characterised by a deficiency of adrenocortical hormones and an excess of steroid precursors. A deficiency of 21-hydroxylase is the most common type, constituting 90% of the cases. The authors hereby, report a case of a one-month-old baby who presented to the Paediatric Emergency Department with typical features of the salt-wasting form of CAH. The diagnosis was confirmed with elevated levels of 17-hydroxyprogesterone and a Cytochrome P450 Family 21 Subfamily A Member 2 (CYP21A2) gene mutation. The child was managed with hydrocortisone, fludrocortisone and salt supplementation, along with symptomatic and supportive care. The child is still under regular follow-up and is doing well.

Cystic fibrosis (CF) is an autosomal recessive disease caused by the inheritance of two mutant cystic fibrosis transmembrane conductance regulator (CFTR) alleles, one from each parent. Autosomal recessive disorders are rarely associated with germline mutations or mosaicism. Here, we propose a case of paternal germline mutation causing CF. The subject also had an identifiable maternal mutant allele. We identified the compound heterozygous variants in the proband through Sanger sequencing, and in silico studies predicted functional effects on the protein. Also, short tandem repeat markers revealed the de novo nature of the mutation. The maternal mutation in the CFTR gene was c.1000C > T. The de novo mutation was c.178G > A, p.Glu60Lys. This mutation is located in the lasso motif of the CFTR protein and, according to in silico structural analysis, disrupts the interaction of the lasso motif and R-domain, thus influencing protein function. This first reported case of de novo mutation in Asia has notable implications for molecular diagnostics, genetic counseling, and understanding the genetic etiology of recessive disorders in the Iranian population. Plain language summary: Identifying the first de novo mutation in the cystic fibrosis transmembrane conductance regulator protein in Iran: a case report with insights from microsatellite markers A child can develop Cystic Fibrosis (CF) if both parents pass on mutated genes. In some rare cases, new genetic mutations occur spontaneously, causing CF. This report discusses a unique case where a child has one gene with a spontaneous mutation and inherits another gene mutation from the mother. We used a method called Sanger sequencing to find the two different gene changes in the affected person. We also used computer analysis to predict how these changes might affect the protein responsible for this genetic disease. To confirm that the child's new change is not inherited, we used a type of genetic marker called microsatellite markers. The mutation inherited from the mother and the new spontaneous mutation resulted in a unique change in the responsible protein. This mutation is located in a specific part of the protein called the lasso motif. Our computer simulations show that this mutation disrupts the interaction between the lasso motif and another part of the protein called the R-domain, which ultimately affects the protein's function. This case is significant because it is the first reported instance of a de novo mutation causing CF in Asia. It has important implications for genetic testing, counseling, and understanding how recessive genetic disorders like CF occur within the Iranian population. [ABSTRACT FROM AUTHOR]

Autosomal recessive disorders, including Tay-Sachs disease, cystic fibrosis, phenylketonuria (PKU), and sickle cell anemia, are significant genetic diseases worldwide. This paper explores their genetic mutations, clinical manifestations, and inheritance patterns. TaySachs disease results from HEXA gene mutations, causing nerve cell ganglioside accumulation. Cystic fibrosis arises from CFTR gene mutations, leading to mucus buildup. PKU stems from PAH gene mutations, causing phenylalanine accumulation and neurological issues. Sickle cell anaemia, caused by HBB gene mutations, leads to abnormal haemoglobin production and red blood cell deformation. Understanding these disorders' genetic basis is vital for accurate diagnosis and treatment development. Advanced genetic testing techniques, like next-generation sequencing, enable early diagnosis and personalized interventions. Ongoing research seeks to understand the interplay of genetic, environmental, and epigenetic factors in disease progression. [ABSTRACT FROM AUTHOR]

Aminoacyl-tRNA synthetases play a pivotal role in catalyzing the precise coupling of amino acids with their corresponding tRNAs. Among them, Tyrosyl tRNA synthetase, encoded by the YARS1 gene, facilitates the aminoacylation of tyrosine to its designated tRNA. Heterozygous variants in the YARS1 gene have been linked to autosomal dominant Charcot-Marie-Tooth type C, while recent findings have unveiled biallelic YARS1 variants leading to an autosomal recessive multisystemic disorder in several cases. In this report, we present a novel case characterized by dysmorphic facies, and multisystemic symptoms, prominently encompassing neurological issues and a microarray conducted shortly after birth revealed 47, XXY. Utilizing whole exome sequencing, we uncovered a paternally inherited likely pathogenic variant (c.1099C > T, p.Arg367Trp), previously reported, coinciding with the father's history of hearing loss and neurological symptoms. Additionally, a maternally inherited variant of uncertain significance (c.782T > G, p.Leu261Arg), previously unreported, was identified within the YARS1 gene. The observed phenotypes and the presence of compound heterozygous results align with the diagnosis of an autosomal recessive disorder associated with YARS1. Through our cases, the boundaries of this emerging clinical entity are broadened. This instance underscores the significance of comprehensive genetic testing in patients exhibiting intricate phenotypes.

Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive disorders that occur due to defects in steroid synthesis. It is characterised by a deficiency of adrenocortical hormones and an excess of steroid precursors. A deficiency of 21-hydroxylase is the most common type, constituting 90% of the cases. The authors hereby, report a case of a one-month-old baby who presented to the Paediatric Emergency Department with typical features of the salt-wasting form of CAH. The diagnosis was confirmed with elevated levels of 17-hydroxyprogesterone and a Cytochrome P450 Family 21 Subfamily A Member 2 (CYP21A2) gene mutation. The child was managed with hydrocortisone, fludrocortisone and salt supplementation, along with symptomatic and supportive care. The child is still under regular follow-up and is doing well. [ABSTRACT FROM AUTHOR]

Peptidyl-tRNA hydrolase 2 (PTRH2) is an evolutionarily highly conserved mitochondrial protein. The biallelic mutations in the PTRH2 gene have been suggested to cause a rare autosomal recessive disorder characterized by an infantile-onset multisystem neurologic endocrine and pancreatic disease (IMNEPD). Patients with IMNEPD present varying clinical manifestations, including global developmental delay associated with microcephaly, growth retardation, progressive ataxia, distal muscle weakness with ankle contractures, demyelinating sensorimotor neuropathy, sensorineural hearing loss, and abnormalities of thyroid, pancreas, and liver. In the current study, we conducted an extensive literature review with an emphasis on the variable clinical spectrum and genotypes in patients. Additionally, we reported on a new case with a previously documented mutation. A bioinformatics analysis of the various PTRH2 gene variants was also carried out from a structural perspective. It appears that the most common clinical characteristics among all patients include motor delay (92%), neuropathy (90%), distal weakness (86.4%), intellectual disability (84%), hearing impairment (80%), ataxia (79%), and deformity of head and face (~70%). The less common characteristics include hand deformity (64%), cerebellar atrophy/hypoplasia (47%), and pancreatic abnormality (35%), while the least common appear to be diabetes mellitus (~30%), liver abnormality (~22%), and hypothyroidism (16%). Three missense mutations were revealed in the PTRH2 gene, the most common one being Q85P, which was shared by four different Arab communities and was presented in our new case. Moreover, four different nonsense mutations in the PTRH2 gene were detected. It may be concluded that disease severity depends on the PTRH2 gene variant, as most of the clinical features are manifested by nonsense mutations, while only the common features are presented by missense mutations. A bioinformatics analysis of the various PTRH2 gene variants also suggested the mutations to be deleterious, as they seem to disrupt the structural confirmation of the enzyme, leading to loss of stability and functionality. [ABSTRACT FROM AUTHOR]

Abstract Background Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare disease with a high mortality rate caused by VPS33B or VIPAS39 mutations. ARC syndrome typically presents with arthrogryposis, renal tubular leak and neonatal cholestatic jaundice, and most patients with this disease do not survive beyond one year. Case presentation Here, we report the case of a 13-year-old girl with ARC featuring an incomplete and mild phenotype with novel compound heterozygous mutations of VPS33B. The patient presented with arthrogryposis (claw-shaped limbs), ichthyosis, jaundice, and pruritus. Laboratory tests revealed highly evaluated levels of total bilirubin (TB), direct bilirubin (DB), and total bile acid (TBA) as well as normal levels of gamma-glutamyltransferase (GGT). However, signs of renal dysfunction, as well as other manifestations of ARC syndrome, including nervous system abnormalities, deafness, and failure to thrive, were not observed. The patient’s clinical symptoms of jaundice and pruritus were significantly alleviated by administration of ursodeoxycholic acid. Whole-exome sequencing (WES) revealed novel compound heterozygous mutations of VPS33B, c.1081 C > T (p.Q361X,257)/c.244 T > C (p.C82R). Both variants were predicted to be pathogenic in silico and have never been reported previously. To date, the patients’ cholestatic jaundice has been well controlled with continuous treatment of ursodeoxycholic acid. Conclusions We report the case of a Chinese female with ARC including novel compound heterozygous mutations of VPS33B and an incomplete and mild phenotype. Early diagnosis and suitable symptomatic therapies are critical for the management of ARC patients with mild manifestations and prolonged lifespan.

We present a fetus with bilaterally enlarged and echogenic kidneys. Prenatal testing detected compound heterozygosity for a 0.676 Mb de novo deletion and an inherited pathogenic variant in PKHD1. This is the first case of autosomal recessive polycystic kidney disease (ARPKD) with a prenatally detected disease‐causing PKHD1 deletion. [ABSTRACT FROM AUTHOR]

A homozygous individual for ITGB7 gene mutation, an autosomal recessive congenital disorder in Holstein cattle, was retrospectively identified by genotyping of 195 stored blood from patients less than 12 months of age. Other 24 patients (12.3%) showed heterozygous. The homozygous individual was a 107-day-old female calf born on March 2017, who presented with chronic diarrhea and severe hypocholesterolemia suggesting hereditary cholesterol deficiency (CD), but genotyping analysis showed negative for CD. The patient showed watery diarrhea, dehydration, and extreme emaciation. Necropsy revealed no apparent cause of chronic diarrhea. Histopathological examination revealed mild mucosal inflammation from the jejunum to the colon. Seven years after the patient's death, the availability of ITGB7 gene mutation testing revealed the patient to be homozygous.

Wilson disease is one of the uncommon, hereditary, slowly progressing, and autosomal recessive diseases that cause motion disorders. The pathogenesis of Wilson disease is attributed to the accumulation of copper in different parts of body mainly the brain, eyes, liver, etc. due to the mutation taking place in the ATP7B gene. This disease thus leads to dysfunction of liver, neurons, brain, eyes and infertility. Thus, there is a need of proper treatment for this disease. There are numerous treatments available, including penicillamine, zinc, ammonium tetrathiomolybdate, trientine, and combination drugs; however, these treatments have a variety of side effects and poor pharmacokinetics, leading to the approval of trientine salts, of which trientine tetrahydrochloride was found to be an efficient, safe, and drug with few side effects. In this review, various aspects related to the disease and trientine salts have been summarized including the pathogenesis of Wilson disease, treatments of Wilson disease, mechanism of trientine as well as comparative pharmacokinetics with the safety and efficacy of both the salts of trientine. We have also tried to explain the preference of usage of trientine tetrahydrochloride over trientine dihydrochloride with some drugs in clinical trials. Here various factors that lead to treatment failure and consideration of alternate therapies have been discussed. Clinical trials and investigations are still going on over gene therapy and stem cells usage in the treatment of Wilson disease which can be used as an effective treatment in future.

Keywords: High myopia; autosomal recessive disorder; Poretti-Boltshauser syndrome; retinal dystrophy; cerebellar cysts EN High myopia autosomal recessive disorder Poretti-Boltshauser syndrome retinal dystrophy cerebellar cysts 653 657 5 09/29/22 20221001 NES 221001 Introduction Poretti-Boltshauser syndrome (OMIM 150320) (PTBHS) is an autosomal recessive disorder characterized by specific cerebellar abnormalities including cerebellar dysplasia with cysts, enlarged fourth ventricle, and vermis hypoplasia. Micalizzi et al. found ocular motor apraxia in 13 out of 17 patients, strabismus in 7 out of 17 patients, and nystagmus in 5 patients ([1]). High myopia and vitreal veils in a patient with Poretti- Boltshauser syndrome due to a novel homozygous LAMA1 mutation The patient presented with high myopia and vitreous veils, phenotype usually seen in the vitreo-retinopathies such as Stickler and Wagner syndrome, indicating the role of I LAMA1 i (laminin alpha-1) in the development of these structures. [Extracted from the article]

Background: Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare disease with a high mortality rate caused by VPS33B or VIPAS39 mutations. ARC syndrome typically presents with arthrogryposis, renal tubular leak and neonatal cholestatic jaundice, and most patients with this disease do not survive beyond one year.Case Presentation: Here, we report the case of a 13-year-old girl with ARC featuring an incomplete and mild phenotype with novel compound heterozygous mutations of VPS33B. The patient presented with arthrogryposis (claw-shaped limbs), ichthyosis, jaundice, and pruritus. Laboratory tests revealed highly evaluated levels of total bilirubin (TB), direct bilirubin (DB), and total bile acid (TBA) as well as normal levels of gamma-glutamyltransferase (GGT). However, signs of renal dysfunction, as well as other manifestations of ARC syndrome, including nervous system abnormalities, deafness, and failure to thrive, were not observed. The patient's clinical symptoms of jaundice and pruritus were significantly alleviated by administration of ursodeoxycholic acid. Whole-exome sequencing (WES) revealed novel compound heterozygous mutations of VPS33B, c.1081 C > T (p.Q361X,257)/c.244 T > C (p.C82R). Both variants were predicted to be pathogenic in silico and have never been reported previously. To date, the patients' cholestatic jaundice has been well controlled with continuous treatment of ursodeoxycholic acid.Conclusions: We report the case of a Chinese female with ARC including novel compound heterozygous mutations of VPS33B and an incomplete and mild phenotype. Early diagnosis and suitable symptomatic therapies are critical for the management of ARC patients with mild manifestations and prolonged lifespan. [ABSTRACT FROM AUTHOR]

الملخص: إن حالة انقلاب وضع الأحشاء الكامل هو اضطراب وراثي جيني متنحي، ولكن في حالات التوائم المتطابقة يمكن أن يكون مرتبط بكروموسوم اكس. يكون التفاف الأعضاء الداخلية بالبطن ب ٢٧٠ درجة عكس عقارب الساعة. تكون الجراحات بالمنظار للمرضى الذين يعانون من انقلاب وضع الأحشاء الكامل غالبا أصعب من المرضى الطبيعيين نتيجة لانعكاس الوضع التشريحي. نستعرض في هذا التقرير حالة سمنة مفرطة (مؤشر كتلة الجسم ٣٦ كجم/متر مربع) تعاني من انقلاب وضع الأحشاء الكامل، وأجريت لها جراحة تكميم المعدة بنجاح. نحن نقدم في هذا التقرير كل التفاصيل التقنية والصعوبات أثناء إجراء هذه العملية. نعتقد أن جراحة تكميم المعدة عندما تكون بواسطة خبير في جراحات المناظير فإنها تكون مجدية وفاعلة وآمنة في حالات انقلاب وضع الأحشاء الكامل. Abstract: Situs inversus totalis (SIT) is a rare genetic autosomal recessive disorder; however, in identical twins, it may be misinterpreted as X-linked disorder. SIT describes a 270° counterclockwise rotation of the intra-abdominal organs. Laparoscopic surgery in patients with SIT may be more difficult than in normal patients due to its mirror image anatomy. We report a case of a morbidly obese patient (body mass index 36 kg/m2) with SIT who underwent successful laparoscopic sleeve gastrectomy. This article describes all technical details and difficulties of this operation due to the presence of SIT. When performed by an expert laparoscopic surgeon, however, laparoscopic sleeve gastrectomy appears to be a feasible, effective, and safe procedure to treat morbidly obese patients with SIT.

Alkaptonuria (AKU) is a rare autosomal recessive disorder caused by homogentisc acid (HGA) accumulation, the deposition of which in the joints usually causes ochronotic arthropathy. With no specific therapy for AKU currently, total joint arthroplasty in ochronotic arthropathy is applied to relieve the symptoms. A 63-year-old female patient came to our Orthopedic Surgery Department in 2019, complaining of severe limitation of movement and pain in the right hip for more than one year. A right total hip arthroplasy (THA) was performed due to the ineffective conservative therapy. At a follow-up of more than 15 months, the woman had full mobility with no complaining of pains. Since there is no relevant case reported about THA therapy for Chinese AKU patients, this report provides a feasible scheme, which makes clinical data more comprehensive.

Abstract Background Progressive familial intrahepatic cholestasis (PFIC) is a group of genetic autosomal recessive disorders that predominantly affects young children and results in early-onset progressive liver damage. Several types of PFIC were defined based on different genetic aetiologies in last decades. Case presentation Here, we report a Chinese young child diagnosed as PFIC with variants in tight junction protein 2 (TJP2). The patient was affected by a long history of jaundice, pruritus, and failure to thrive. Highly elevated level of serum total bile acid (TBA) and normal levels of gamma-glutamyltransferase (GGT) were observed at hospitalization. The patient’s clinical symptoms could be alleviated by administration of ursodeoxycholic acid. Genetic testing by next generation sequencing (NGS) found novel compound heterozygote mutations c.2448 + 1G > C/c.2639delC (p.T880Sfs*12) in TJP2, which were inherited from her mother and father, respectively. Both mutations were predicted to abolish TJP2 protein translation, and neither has previously been identified. Conclusion We report a Chinese female PFIC child with novel compound heterozygous mutations of TJP2. Genetic testing by NGS is valuable in the clinical diagnosis of hereditary liver disease.

Ellis van Creveld syndrome (EVC) is a rare autosomal recessive disorder also called chondroectodermal dysplasia. This study reports on a 40‐year‐old woman from Iran with a syndromic appearance consisting of a coarse face, conical anterior teeth, dental agenesis and permanent teeth at birth, several small extralabial, nonmidline frenula with a high‐arched palate, and a large maxillary labial frenulum. The patient had cyanosis on her lips since childhood and a history of adenoid tonsillectomy surgery. She also had androgenic alopecia, an elongated trunk with excessive lordosis and pectus excavatum, polycystic ovarian syndrome, and a history of two periods in a month. She also had multiple fibrocystic cysts in her breasts, lower extremity deformity, dysplastic genu valgum, and short limb dwarfism; she had undergone left knee surgery four times and had severe osteoporosis in some of her bones and some hyperpigmented patches on the dorsal of the left hand. Her hands and feet were also wide and markedly deformed with hypoplastic fingernails and toenails, and she had bimanual hexadactyly on the ulnar side of the hands. She also had a history of severe hypotension and cyanosis during surgery and suffered from congenital heart failure and had undergone open heart surgery for correcting her atrial heart defect. In this study pectus excavatum, Phrygian cap gallbladder, liver hemangioma, polycystic ovarian disease, and breast fibrocystic cysts was reported for first time in this case of EVC syndrome. This case was reported and all articles regarding common, uncommon, rare, and extremely rare presentations of this syndrome were reviewed. [ABSTRACT FROM AUTHOR]

Parahaemophilia or Owren's diseaseis a rare haemorrhagic disorder occurs due to congenital and frequently familial deficiency of Factor V.It is characterized by epistaxis, bruising, mucosal bleeding, soft tissue bleeding and haemarthrosis. We report a case of 6 year old female patient with overlapping features with other haemorrhagic disorder. With the complaints of recurrent episodic per rectal bleeding, patient was evaluated at different hospitals in Chattagram and was diagnosed as a case of Haemophilia B and treated accordingly. As her condition was not improved expectedly, she was referred to Armed Forces Institute of Pathology (AFIP) for further evaluation. The lab tests showed prolongation of prothrombin time (PT) and activated partial thromboplastin time (APTT), with normal bleeding time (BT) and thrombin time (TT). Coagulation factors assay revealed a significant decrease of factor V, 1% of normal range. Other coagulation factors are normal. She was treated with FFP and recovered four weeks after treatment. [ABSTRACT FROM AUTHOR]

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This case report represents an infant who presented with typical clinical and biochemical features of ISH with a progressive and disabling joint pain and contractures leading to eventual death at age the of 6 months from severe chest infection and diarrhea.ISH is a rare autosomal recessive disease that involves deposition of hyaline material in multiple tissues throughout the body, resulting in joint contractures, subcutaneous nodules, diarrhea, and growth failure.ISH typically presents between birth and 6 months of age. It is equally common in males and females. While described in many ethnic groups, it has most commonly been seen in children of Turkish, Indian, and Moroccan descent. ISH being autosomal recessive disorder, awareness has to be raised to by explaining the risk of recurrence in future siblings being 25%. Prenatal diagnosis is possible by fetal DNA analysis at around 12 to 16 weeks of pregnancy. To conclude, the prognosis of ISH is poor and most treatments have not proved beneficial. Physical therapy and nutritional support may improve quality of life. Awareness and early diagnosis of the disease, recognition that joint contractures are painful, and control of pain will lead to decreased invasive testing and increased patient comfort. Correct diagnosis of disease using clinical findings and genetics studies are important for family planning and counseling. [ABSTRACT FROM AUTHOR]

Abstract Background Glutaric aciduria type II (GA II) is an autosomal recessive disorder affecting fatty acid and amino acid metabolism. The late-onset form of GA II disorder is almost exclusively associated with mutations in the electron transfer flavoprotein dehydrogenase (ETFDH) gene. Till now, the clinical features of late-onset GA II vary widely and pose a great challenge for diagnosis. The aim of the current study is to characterize the clinical phenotypes and genetic basis of a late-onset GAII patient. Methods In this study, we described the clinical and biochemical manifestations of a 23-year-old female Chinese patient with late-onset GA II, and performed genomic DNA-based PCR amplifications and sequence analysis of ETFDH gene of the whole pedigree. We also used in-silicon tools to analyze the mutation and evaluated the pathogenicity of the mutation according to the criteria proposed by American College of Medical Genetics and Genomics (ACMG). Results The muscle biopsy of this patient revealed lipid storage myopathy. Blood biochemical test and urine organic acid analyses were consistent with GA II. Direct sequence analysis of the ETFDH gene (NM_004453) revealed compound heterozygous mutations: c.250G > A (p.A84T) on exon 3 and c.920C > G (p.S307C) on exon 8. Both mutations were classified as “pathogenic” according to ACMG criteria. Conclusions In conclusion, our study described the phenotype and genotype of a late-onset GA II patient, reiterating the importance of ETFDH gene screening in these patients.

Recessive missense mutation in the solute carrier family 12, member 1 (SLC12A1 ) gene (g.62382825G>A) is associated with hydrallantois, which is the accumulation of fluid in the allantoic cavity of a pregnant animal, and usually causes fetal death in Japanese Black cattle. However, the symptoms of a homozygote with this mutation that do not result in fetal death have not previously been tracked and evaluated. In the present study, we observed a homozygote with the SLC12A1 risk allele over a long‐term period. The calf did not show any obvious clinical symptoms, although it did exhibit a slight growth retardation that accompanied mild calciuria. At 28 months of age, the homozygote showed renal dysfunction, which in turn resulted in hydronephrosis. The time course of the symptoms was consistent with the phenotype of Bartter syndrome in humans. Additionally, the risk heterozygous genotype did not any effects on carcass traits, which indicates that eliminating the risk allele would not have any unfavorable effects. Therefore, we emphasize that both the fetal‐ and late‐stage symptoms associated with the SLC12A1 risk allele compromise animal welfare, and consequently may result in severe economic losses for individual farmers if the SLC12A1 risk allele is not eliminated from the population. [ABSTRACT FROM AUTHOR]

Objectives: To find the association between consanguinity and frequency of b-thalassemia and to assess the knowledge of parents regarding disease as well as inclination towards premarital carrier screening (PMCS), pre natal diagnosis, pre conception genetic counseling. Study Design: A retrospective cohort study. Setting: Patients with beta thalassemia attending Fatimid Foundation and PNS Shifa Hospital, Karachi. Period: Six Months July - December, 2017. Materials and Methods: Data was collected by pre tested questionnaire which include basic demographic profile, frequency of consanguineous marriages and knowledge regarding disease from parents of children suffering from thalassemia. The study was approved by ethical review committee. Data was analyzed using SPSS version 21. Chi square test was applied. Results: Data was collected from 200 study participants including parents of thalassemia. Males were 52% and 48% were the females. 78.5% were relatives (p=0.001) out of these related, first degree relatives were 61% and 17.5% were distant relatives (p 0.009). Only 25% were aware of genetic counseling, 65% know that thalassemia had genetic mode of transmission (p=0.005), 24% were aware of screening modalities available for thalassemic patients (p=0.001). About 63.55% agreed that premarital screening can prevent thalassemia (p=0.001), majority (83%) of parents were not aware of pre natal diagnosis of thalassemia (p=0.001) more than half of study participants (52%) were still in favor of cousin marriages in future. Conclusion: Thalassemia was found most prevalent among first degree familial relatives. Parents have inadequate knowledge regarding disease. Lack of knowledge and trends consanguineous marriages are strong contributory factor for causation of disease. [ABSTRACT FROM AUTHOR]

The Bardet-Biedl Syndrome (BSS) is a genetic disease based on autosomal recessive disorder characterised by non-allelic heterogeneity. The prevalence in the European population is only 1 in 160,000 live births. We observed a case of late diagnosis in a patient of 59 years. Different medical specialists, who had seen him before his admission to the hospital, separately treated his different signs and symptoms. The patient was genetically investigated with successfully confirmation of the clinical diagnosis of Bardet-Biedl syndrome was done. This case report underlines the importance of an overview of different clinical signs and symptoms and how different specialties need to collaborate to allow early diagnosis of the diseases.

Introduction and Importance: Ataxia telangiectasia (A-T) is a rare autosomal recessive neurodegenerative disorder with early childhood onset. It is characterized by ataxia, oculocutaneous telangiectasia, immunodeficiency, and lymphoid-origin cancer predisposition due to ataxia telangiectasia mutated gene mutations., Case Presentation: The authors present a 19-year-old girl with spastic movements since 18 months, leading to wheelchair dependence. Ocular telangiectasia, dystonic posture, and slurred speech were evident. Diagnosis involved elevated alpha-fetoprotein levels and typical brain imaging., Clinical Discussion: A-T due to ataxia telangiectasia mutated gene mutations located on chromosome 11q22-23. It has varied presentations categorized by age and features. Timely diagnosis relies on characteristic symptoms, lab findings, and imaging. Radiation sensitivity and increased cancer risk underscore cautious radiation use., Conclusion: A-T is a complex disorder with no cure. Genetic counseling for parents is vital. Its poor prognosis due to infection susceptibility and cancer risk necessitates supportive care. Comprehensive management, including genetic counseling and careful surveillance, is imperative., Competing Interests: Authors have no conflict of interest to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

AbstrakSingle Nucleotide Polymorphism (SNP) merupakan variasi genetik yang ditemukan pada lebih dari 1% populasi. Haplotipe, yang merupakan sekelompok SNP atau alel dalam satu kromosom, dapat di turunkan ke generasi selanjutnya dan dapat digunakan untuk menelusuri gen penyebab penyakit (marker genetik). Artikel ini bertujuan menjelaskan aplikasi analisis SNP dalam diagnosis beberapa sindrom yang disebabkan gangguan genetik. Berdasarkan laporan studi terdahulu, sindrom yang disebabkan oleh UPD (uniparental disomy) maupun penyakit autosomal resesif yang muncul sebagai akibat perkawinan sedarah dapat dideteksi dengan SNP array melalui analisis block of homozygosity dalam kromosom. Kelebihan lain SNP array adalah kemampuannya dalam mendeteksi mosaicism level rendah yang tidak terdeteksi dengan pemeriksaan sitogenetik konvensional. Bahkan saat ini, SNP array sedang diujicobakan dalam IVF untuk mendapatkan bayi yang sehat. Hal ini dapat dilakukan dengan mendeteksi ada atau tidaknya gen tunggal penyebab penyakit pada embrio hasil bayi tabung sebelum embrio ditanamkan ke uterus. Analisis SNP dengan SNP array mempunyai banyak kelebihan dibanding metode pemeriksaan SNP lainnya dan diharapkan dapat digunakan secara luas dalam bidang diagnostik molekuler genetik di masa mendatang.AbstractSingle Nucleotide Polymorphism (SNP) is a genetic variant with a frequency of >1% of a large population. Haplotypes, a combination of a set of SNPs/alleles that appear as “associated blocks” on one chromosome, tend to be inherited together to the next offspring and can be used as genetic markers to trace particular diseases. This article aimed at explaining of SNP analysis application in diagnosis of genetic-disorder related syndrome. Previous studies showed that syndromes caused by UPD or autosomal recessive disorder as a result of consanguineous marriage can be identified by SNP array through analysing block of homozygosity region in a chromosome. Another advantage of SNP arrays is its ability in detecting low level mosaicism which was unidentified by conventional cytogenetic examination. Nowadays, SNP arrays are included in IVF process to obtain a healthy baby. It can be done by detecting the absence or the presence of disease-causing single gene in an embryo before it implanted to the womb. SNP analysis with SNP array has many advantages over other SNP analysis methods and is therefore expected can be widely used in the future in the field of molecular diagnostic.

C57BL/6J (B6J) is the most widely used mouse strain for metabolic research. It carries a spontaneous mutation in the nicotinamide nucleotide transhydrogenase (Nnt) gene. This study compared blood glucose levels in B6J and Kunming (Km) mice as control. It was observed that blood glucose levels in B6J and Km mice at 4 weeks of age decreased post feeding and reached the lowest level at 24 hr of fasting. Blood glucose was significantly higher in B6J mice than that in Km mice at 0 hr, 2 hr and 10 hr of fasting. In addition, the correlation between the Nnt gene, growth traits and the feed conversion efficiency ratio (FCR) in (B6J × Km) F2 generation (N = 342) was also analyzed. We found that Nnt was significantly associated with body weight at 3 weeks (IBW) (P<0.01) and 5 weeks (FBW) (P<0.05) and average metabolic body weight (AMBW) (P< 0.01) but was not associated with average daily feed intake (AFI), average daily gain (ADG) and FCR. Furthermore, qRTPCR revealed that the expression levels of Glut-1, Glut-2, Akt-1, Irs-1 and Ucp-2 genes were significantly different in high and low-FCR mice. Our study offers novel evidence of the roles of Nnt gene in metabolism and growth. [ABSTRACT FROM AUTHOR]