Search

Neurodevelopmental disorder with microcephaly, ataxia, and seizures (NEDMAS) syndrome is a rare neurodevelopmental disorder characterized by moderate intellectual disability (ID), thin body habitus, microcephaly, seizures, ataxia, muscle weakness, and speech impairment. So far, only two families with NEDMAS have been reported. We report the clinical and molecular characteristics of three unrelated Turkish families with four NEDMAS patients. Whole-exome sequencing was used to search for the disease-causing variant. The main manifestations of the probands are severe developmental delay and ID, thin body habitus, and severe hypotonia. Brain imaging revealed bilateral cerebral and cerebellar diffuse atrophy. Sequencing results showed that both patients carried a novel missense variant c.1196C>T (p.Thr399Met) in the seryl-tRNA synthetase gene. Our findings help expand the variant spectrum of NEDMAS and provide additional information for diagnosing cases with atypical features. © 2022 Lippincott Williams and Wilkins. All rights reserved.

Purpose: Familial Mediterranean Fever (FMF) is a hereditary auto inflammatory disease (MIM#249100). The most common symptoms are high fever, abdominal pain and arthralgia. FMF is the result of variations in the MEditerraneanFeVer (MEFV) gene, which is located on chromosome 16p13.3, consists of 10 exons and encodes the pyrin (marenostrin) protein. The frequency of MEFV gene variants that cause FMF varies according to ethnic groups, countries and even different regions in the same country. In this study, we aimed to determine the frequency and distribution of MEFV gene alterations that cause Familial Mediterranean fever in southeastern Turkey. Materials and Methods: A total of 6,660 patients with a prediagnosis of FMF, including 3,495 women and 3,165 men, were included in the study. Fragment analysis was performed to investigate the MEFV gene variations of the patients and the 19 most common variants in the Turkish population were examined. Results: We found at least one variation in 50.17% (3,341) of our 6,660 patients. In our patients, 108 different genotypes; in Exon 2, 3, 5 and 10 and we identified 16 different variations. We found 2,120 (63.21%) patients heterozygous, 693 (20.74%) compound heterozygotes, 275 (8.23%) homozygous and 261 (7.81%) complex genotypes. The 5 variants with the highest allele frequency are respectively; R202Q (27.84%), M694V (22.83%), E148Q (21.98%), V726A (7.42%), and M680I(G>C) (6.39%). Conclusion: We identified the most common prevalence of MEFV gene alteration in a large patient group in our region. High R202Q mutation rates were among the remarkable results of this study.

Nicolaides-Baraitser syndrome (NCBRS) (OMIM 601358) is an uncommon but well-recognized autosomal dominant entity that is characterized by sparse scalp hair, characteristic coarse facies, microcephaly, seizures, developmental delay, intellectual disability (ID) and prominence of the interphalangeal joints and distal phalanges. Seizures are also common finding besides developmental delay and ID, which is severe approximately in half, moderate in one third and mild in the remainder. Here, we report two Turkish patients with NCBRS. One has a novel variant [NM_003070.5:c.3389G>T p.(Gly1130Val)] and a mild-moderate phenotype, and the other has a known variant [NM_003070.5:c.2554G>A p.(Glu852Lys)] correlated with severe phenotype.

Background: Chromosomal microarray is considered as the first-line diagnostic genetic test in all individuals with intellectual disability (ID) and attention-deficit disorders. In recent years, the use of chromosomal microarrays routinely for this purpose has resulted in the identification of many new microdeletion and microduplication regions connected with these clinical situations, including the 1q21.1 and 14q32.2q32.31 microdeletions. Case Presentation: A 5-year-old male patient came to the clinic because of ID, hyperactivity, growth retardation, and speaking difficulty. We determined strabismus on both the eyes, and he was myopic. He had a high palate, little, and sparse teeth. On the right hand, there was a simian line. Both undescended testes were brought down with surgery. In addition, he had got an inward penis head. He had joint laxity in most of the joints. He had pes planus and talipes valgus. Therefore, we decided to make array-comparative genomic hybridization analysis and the result came 1368.001 kb deletion on 1q21.1 between chr1: 146023922 and 147391923 nucleotides and 992.003 kb deletion on 14q32.2q32.31 between chr14: 100453009 and 101445012 nucleotides according to �Human Genome Build 37� (The result was confirmed by a fluorescent in situ hybridization method performed to determine the particular deleted regions). Conclusion: Here, we report the first case presented with ID, hyperactivity, growth retardation, and speaking difficulty with other findings and has a combination of de novo 1q21.1 and 14q32.2q32.31 microdeletions. Although several research groups have reported similar results with similar regions separately, this study is the first of its kind revealing the effects of this combination to clinical outcome.

Hereditary spastic paraplegias (HSP) are a group of inherited, neurodegenerative disorders characterized by progressive gait impairment, lower extremity spasticity and increased patellar reflexes. More than 80 types of HSP have been defined to date. In complicated forms, lower limb spasticity and gait impairment is accompanied by an additional neurological finding. Autosomal recessive (AR) HSPs are usually identified in complicated forms and occur more frequently in countries where consanguineous marriage is more widespread. Next generation sequencing techniques, developed in the last decade, have led to the identification of many new types of HSP and reduced the diagnostic odyssey. Whole exome sequencing (WES) can diagnose up to 75% of undiagnosed HSP patients. Targeted genetic analysis with good clinical phenotyping gives the best diagnostic yields for rare diseases. Clinical heterogeneity is prominent in AR complicated HSP. However, some clinical features complicating the disease or magnetic resonance imaging findings, including thin corpus callosum or white matter abnormalities, can help to distinguish some types. AR spastic paraplegia type 64 (SPG64) is a very rare HSP, caused by a mutation in the ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) gene, first described in 2014. To date only nine patients from five families have been reported. We present two siblings with a novel pathogenic variant in ENTPD1, diagnosed by WES, as the sixth published family. We propose that early onset in childhood, cognitive impairment, dysarthria/anarthria, dystonia and areflexia may be the distinctive features of SPG64 and more clinical evidence from families with pathogenic ENTPD1 variants is warranted.

The goal of this study was to assess genes known to be associated with tooth agenesis with next-generation sequencing (NGS) and analyze the relationship between these mutations and tooth agenesis phenotypes.The study included 49 individuals aged between 6 and 13 years. A total of 14 genes related to nonsyndromic tooth agenesis were selected for targeted NGS. Mutations in Msh homeobox 1 (MSX1), Wnt family member 10A (WNT10A), axis inhibition protein 2 (AXIN2), keratin 17 (KRT17), lipoprotein receptor 6 (LRP6), and secreted protein, acidic and rich in cysteine (SPARC)-related modular calcium-binding protein 2 (SMOC2) genes were investigated.Mutations in six genes were detected in 12 of 49 subjects. Fifteen variants were identified, including the unknown variants c.657G C in MSX1, c.2029C T in AXIN2, and c.1603A T in LRP6. Second premolar tooth agenesis was observed in 43.3% of all tooth agenesis cases with mutations, and it was the predominant phenotype observed for each mutated gene, followed by tooth agenesis of the lateral incisors (20%).Variations in MSX1, WNT10A, AXIN2, KRT17, LRP6, and SMOC2 may be a risk factor for hypodontia or oligodontia in the Turkish population.ZIELSETZUNG: Ziel dieser Studie war es, als assoziiert mit Zahnagenesien bekannte Gene mittels NGS („next-generation sequencing“) zu untersuchen und den Zusammenhang zwischen diesen Mutationen und dem Phänotyp der Zahnagenesie zu analysieren.In die Studie wurden 49 Personen im Alter zwischen 6 und 13 Jahren eingeschlossen. Insgesamt wurden 14 mit nichtsyndromaler Zahnagenesie assoziierte Gene für ein gezieltes NGS ausgewählt. Untersucht wurden Mutationen in den Genen MSX1 („Msh homeobox 1“), WNT10A („Wnt family member 10A“), AXIN2 („axis inhibition protein 2“), KRT17 („keratin 17“), LRP6 („lipoprotein receptor 6“) und SMOC2 („SPARC[„secreted protein, acidic and rich in cysteine“]-related modular calcium-binding protein 2“).Mutationen in 6 Genen wurden bei 12 von 49 Probanden nachgewiesen. Fünfzehn Varianten wurden identifiziert, darunter die unbekannten Varianten c.657G C in MSX1, c.2029C T in AXIN2, and c.1603A T in LRP6. Eine Agenesie der zweiten Prämolaren wurde in 43,3 % aller Fälle mit Mutationen beobachtet und war der vorherrschende Phänotyp für jedes mutierte Gen, gefolgt von einer Agenesie der seitlichen Schneidezähne (20 %).Variationen in MSX1, WNT10A, AXIN2, KRT17, LRP6 und SMOC2 können ein Risikofaktor für Hypodontie oder Oligodontie in der türkischen Bevölkerung sein.

Warburg-Micro syndrome (WARBM) is a rare autosomal recessively inherited neuro-ophthalmologic syndrome. Although WARBM shows genetic heterogeneity, the pathogenic variants in RAB3GAP1 were the most common cause of WARBM. In this study, we aimed to evaluate the detailed clinical and dysmorphic features of seven WARBM1 patients and overview the variant spectrum of RAB3GAP1 in comparison with the literature who were referred due to congenital cataracts. A previously reported homozygous variant (c.2187_2188delGAinsCT) was identified in three of these patients, while the other four had three novel variants (c.251_258delAGAA, c.2606+1G>A, and c.2861_2862dupGC). Congenital cataract and corpus callosum hypo/agenesia are pathognomonic for WARBM, which could be distinguished from other similar syndromes with additional typical dysmorphic facial features. Although there is no known phenotype and genotype correlation in any type of WARBM, RAB3GAP1 gene analysis should be previously requested as the first step of genetic diagnosis in clinically suspicious patients when it is not possible to request a multi-gene panel. © 2021 Wiley Periodicals LLC.

Amaç: İnfertilite çiftlerin %15’inde görülen bir problemdir. Oligozoospermi ve azoospermi kaynaklı erkek infertilitesi tanısı alanların %30’unun etiyolojisinde genetik nedenler sorumludur. Bu retrospektif çalışmada, merkezimize başvuran infertil erkeklerde yardımcı üreme teknikleri uygulanmadan önce hem kromozomal yapının belirlenmesi hem de Y kromozomu üzerindeki azoospermik faktör (AZF) bölgesinin mikrodelesyonunun belirlenmesi amaçlanmıştır.Gereç ve Yöntem: Laboratuvarımıza rutin analizler için başvuran 675 hasta çalışıldı. Bu hastalardan konvansiyonel sitogenetik yöntemle periferik kandan kromozom analizi yapıldı ve Y kromozom mikrodelesyon belirleme kiti kullanılarak fragman analizi yöntemi ile Y kromozomu mikrodelesyonu araştırıldı.Bulgular: 675 hastanın 75’inde sitogenetik ve 21’inde moleküler, 2’sinde hem sitogenetik hem moleküler düzeyde anomali belirlendi. Anomalili karyotipe sahip hastalarda sayısal ve yapısal (resiprokal ve robertsonian tip translokasyon, inversiyon, ring kromozom gibi) anomaliler saptandı. Y mikrodelesyon belirlenen hastaların 2’sinde AZFa, 1 hastada AZFb, 13 hastada AZFc/d (c+ proksimal c), 6 hastada AZFb/c/d, 1 hastada AZFc/d ve kısmi AZFa bölgelerinde mikrodelesyon saptandı.Sonuç: Çalışmamız kromozom anomalilerinin ve Y kromozomu mikrodelesyonunun erkek infertilitesinin önemli bir nedeni olduğunu ve bu nedenle infertil hastalarda, kromozom analizi ve Y kromozomu mikrodelesyon testlerinin yapılmasının, erkek kaynaklı infertilitenin açıklanmasında gerekliliğini göstermektedir., Purpose: Infertility is a problem seen in 15% of couples. Genetic causes are responsible for the etiology of 30% of those diagnosed with male infertility due to oligozoospermia and azoospermia. In this retrospective study, it was aimed to determine both the chromosomal structure and the microdeletion of the azoospermic factor (AZF) region on the Y chromosome before the application of assisted reproductive techniques in infertile men admitted to our center.Materials and methods: 675 patients who applied to our laboratory for routine analyzes were studied. Chromosome analysis from peripheral blood was performed from these patients with conventional cytogenetic method and Y chromosome microdeletion was investigated by fragment analysis method using Y chromosome microdeletion detection kit.Results: Of 675 patients, 75 had cytogenetic anomalies, 21 had molecular anomalies, and 2 had both cytogenetic and molecular anomalies. Numerical and structural anomalies (such as reciprocal and robertsonian type translocation, inversion, ring chromosome) were detected in patients with anomaly karyotype. Microdeletion was detected in AZFa in 2 patients, AZFb in 1 patient, AZFc/d (c+ proximal c) in 13 patients, AZFb/c/d in 6 patients, and AZFc/d+ partial AZFa in 1 patient.Conclusion: Our study shows that chromosomal abnormalities and Y chromosome microdeletion are important causes of male infertility, and therefore, chromosome analysis and Y chromosome microdeletion tests are necessary to explain male infertility in infertile patients.

Objective: Identification of vector species and determination of physical and ecological features of their breeding places is essential in implementation of scientific based mosquito control activities. In this study, it is aimed to identify Anopheles species by morphological method and determination of physical and ecological characteristics of their breeding places in Sanliurfa territory. Methods: Mosquito larvae were collected between September 29 and October 03, 2009 from determined 9 breeding places in Birecik, Eyyubiye, Haliliye, Harran, Siverek and Viransehir districts of Sanliurfa province where malaria cases had been reported and four instar larvae were identified morphologically according to keys of DuBose ve Curtin (1965), Merdivenci (1984) and Darsie and Samanidou-Vojadjoglou (1997). Essential ecological parameters of water in breeding places were measured. Temperature and dissolved oxygen were measured by using ExStik® DO600 (Extech Instruments-USA); pH and conductivity were measured by using Hanna Instruments 98129 pH / Conductivity /TDS Tester (Hanna Instruments-Germany) and salinity was measured using ExStik®II EC400 Conductivity/TDS / Salinity/Temperature Meter (Extech Instruments-USA). Results: Of the 274 four instar larvae collected, 231 (%84,3) were identified as An. sacharovi and 41 (%14,96) of them were identified as An. superpictus. Two (0,73%) samples identified as Anopheles genus, species discrimination could not be done. In %88,89 (n=8) of nine breeding places An. sacharovi and in %11,11 (n=1) of total breeding places An. superpictus found to be dominant species according to the morphological results. Malaria vector An. sacharovi detected in all breeding places which had different pH values, dissolved oxygen proportions, electrical conductivity, water temperature and salinity proportions with horizontal vegetation. The limits of tolerance for essential ecological parameters of species found to be as: pH-7,77-9,18 (mean 8,53); electrical conductivity-310-1100 (?S/cm) (mean 496,91); dissolved oxygen (mg/l)-1,64-13,06 (mean 9,67); temperature of water-20,3-25,8 °C (mean 23,46); salinity 0,15-0,55 ppt (mean 0,24). The limits of tolerance for essential ecological parameters of An. superpictus species in study area measured as: pH 8,48; electrical conductivity 710 ?S/cm; dissolved oxygen 8,91 mg/l; temperature of water 25,8 °C; salinity 0,35. In statistical analysis of physical and ecological characteristics of mosquito breeding places; no significant difference between pH values (p=0,189) was found between An. sacharovi and An. superpictus breeding places but significant dif¬ference have been found in water temperature (p= 0,0000001), electrical conductivity (p= 0,0000001), salinity (p= 0,0000001) and dissolved oxygen (p= 0,001) values. Conclusion: An. sacharovi is thought to be considered to be primary malaria vector in Sanliurfa Province as it can become the dominant species in malaria endemic areas and also in areas where transmission reoccur due to its ecological flexibility. In this context, vector control strategies in Sanliurfa should be revised and planning should be done according to the characteristics of the vector. © 2020 Refik Saydam National Public Health Agency (RSNPHA). 2-s2.0-85087319686

Cockayne syndrome is a rare autosomal recessive, neurodegenerative disorder characterized by a broad spectrum of clinical symptoms. Herein, we will describe a patient diagnosed with Cockayne syndrome by genetic testing who was also determined to be having Dandy–Walker malformation in brain imaging. In this article, we aimed to highlight the general characteristic findings of Cockayne syndrome and to report the togetherness of these two rare entities.

Congenital bilateral laryngeal paralysis/immobilization is an uncommon condition and has been described as isolated or accompanying to some recognizable syndromes. Heterozygous mutations in the FOXP1 gene (605515) are related with intellectual disability and, language impairment with or without autistic features. Expressive language is more affected than receptive language and more than half of the patients experience oromotor dysfunction and/or feeding difficulties. Here we report a child with severe developmental, speech delay and aphonia which was considered due to bilaterally abductor vocal cord immobility. Interstitial 8700 kbp deletion encompassing FOXP1 gene was detected on 3p13p12 chromosomal region. Although it is known that FOXP1 defects are related to abnormalities in vocal communication, FOXP1-associated laryngomalacia or vocal cord paralysis/immobilization cases have not been reported yet. The FOXP1 defects are considered to be a cause of delay in speech, and it is suggested that vocal cord evaluation should be conducted in suspicious cases.

Germline mutations in PTPN11, the gene encoding the Src-homology 2 (SH2) domain-containing protein tyrosine phosphatase (SHP2), cause Noonan syndrome (NS), a relatively common, clinically variable, multisystem disorder. Here, we report on the identification of five different PTPN11 missense changes affecting residues Leu261 , Leu262 , and Arg265 in 16 unrelated individuals with clinical diagnosis of NS or with features suggestive for this disorder, specifying a novel disease-causing mutation cluster. Expression of the mutant proteins in HEK293T cells documented their activating role on MAPK signaling. Structural data predicted a gain-of-function role of substitutions at residues Leu262 and Arg265 exerted by disruption of the N-SH2/PTP autoinhibitory interaction. Molecular dynamics simulations suggested a more complex behavior for changes affecting Leu261 , with possible impact on SHP2's catalytic activity/selectivity and proper interaction of the PTP domain with the regulatory SH2 domains. Consistent with that, biochemical data indicated that substitutions at codons 262 and 265 increased the catalytic activity of the phosphatase, while those affecting codon 261 were only moderately activating but impacted substrate specificity. Remarkably, these mutations underlie a relatively mild form of NS characterized by low prevalence of cardiac defects, short stature, and cognitive and behavioral issues, as well as less evident typical facial features.

Microcephaly-lymphedema-chorioretinal dysplasia is a rare syndrome in which the component of chorioretinopathy may develop later. We describe two patients with microcephaly-lymphedema-chorioretinal dysplasia syndrome who had characteristic facial features and congenital heart defects. Second patient had also lissencephaly which was very rarely reported before. Int J Clin Pediatr. 2017;6(3-4):42-45 doi: https://doi.org/10.14740/ijcp275w

Hypertrophic cardiomyopathy has the highest incidence rate among genetically inherited cardiac diseases. It develops as a result of mutations in genes in related to the sarcomere protein in cardiac muscle. Generally, this results in asymmetrical hypertrophy. Patients who are symptomatic and have a significantly narrow left ventricular undergo should receive surgical treatment, whereas patients with a sudden cardiac death risk should receive treatment with an implantable cardiac defibrillator. This paper presents an infant with hypertrophic cardiomyopathy who was recently identified as having a mutation that resulted in a deletion-insertion type framework shift in the gene MYBPC3, who had family history of sudden death at a young age, and received myectomy and treatment with an implantable cardiac defibrillator in the same session due to a severely narrowed left ventricular outflow tract.

International audience; The SPECC1L protein plays a role in adherens junctions involved in cell adhesion, actin cytoskeleton organization, microtubule stabilization, spindle organization and cytokinesis. It modulates PI3K-AKT signaling and controls cranial neural crest cell delamination during facial morphogenesis. SPECC1L causative variants were first identified in individuals with oblique facial clefts. Recently, causative variants in SPECC1L were reported in a pedigree reported in 1988 as atypical Opitz GBBB syndrome. Six families with SPECC1L variants have been reported thus far. We report here eight further pedigrees with SPECC1L variants, including a three-generation family, and a further individual of a previously published family. We discuss the nosology of Teebi and GBBB, and the syndromes related to SPECC1L variants. Although the phenotype of individuals with SPECC1L mutations shows overlap with Opitz syndrome in its craniofacial anomalies, the canonical laryngeal malformations and male genital anomalies are not observed. Instead, individuals with SPECCL1 variants have branchial fistulae, omphalocele, diaphragmatic hernias, and uterus didelphis. We also point to the clinical overlap of SPECC1L syndrome with mild Baraitser-Winter craniofrontofacial syndrome: they share similar dysmorphic features (wide, short nose with a large tip, cleft lip and palate, blepharoptosis, retrognathia, and craniosynostosis), although intellectual disability, neuronal migration defect, and muscular problems remain largely specific to Baraitser-Winter syndrome. In conclusion, we suggest that patients with pathogenic variants in SPECC1L should not be described as "dominant (or type 2) Opitz GBBB syndrome", and instead should be referred to as "SPECC1L syndrome" as both disorders show distinctive, non overlapping developmental anomalies beyond facial communalities.

Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder belonging to the group of RASopathies. It is typically characterized by congenital heart defects, short stature, dysmorphic craniofacial features, intellectual disability, failure to thrive, and ectodermal abnormalities such as hyperkeratosis and sparse, brittle, curly hair. CFC syndrome is caused by dominant mutations in one of the four genes BRAF, MEK1, MEK2, and KRAS. Only three familial cases of CFC syndrome have been reported to date, whereas the vast majorities are sporadic cases due to de novo mutations. We report on a fourth familial case with transmission of CFC syndrome from father to son due to a novel heterozygous sequence change c.376A>G (p.N126D) in exon 3 of MEK2 gene. This observation further documents the possibility of vertical transmission of CFC syndrome, which appears to be associated with rare mutations and relatively mild intellectual disability in affected individual. The hypomorphic effect of specific mutations particularly regarding neurocognitive issues may be related to the variable fertility of affected individuals.

Succinate-CoA ligase, ADP-forming, beta subunit (SUCLA2)-related mitochondrial DNA depletion syndrome is caused by mutations affecting the ADP-using isoform of the beta subunit in succinyl-CoA synthase, which is involved in the Krebs cycle. The SUCLA2 protein is found mostly in heart, skeletal muscle, and brain tissues. SUCLA2 mutations result in a mitochondrial disorder that manifests as deafness, lesions in the basal ganglia, and encephalomyopathy accompanied by dystonia. Such mutations are generally associated with mildly increased plasma methylmalonic acid, increased plasma lactate, elevated plasma carnitine esters, and the presence of methylmalonic acid in urine. In this case report, we describe a new mutation in a patient with a succinyl-CoA synthase deficiency caused by an SUCLA2 defect.

Clouston Syndrome (CS) is an ectodermal dyplasia characterized by nail dystrophy and hair defects and inherited in an autosomal dominant trait (OMIM #129500). It is caused by the mutations in GJB6 gene which is encoding connexin 30 (Cx30), a member of connexin family and included in the structure of gap junctions serving in intercellular interactions. In the present paper, a 30-year-old mother and her 3-year-old daughter diagnosed as CS. Seven more family members were also diagnosed as CS compatible with autosomal dominant trait. The disease causing heterozygous mutation c.31G>A (p.G11R) was found by Sanger sequencing in exon 5 of GJB6. The latter mutation had been reported in several different populations yet it is reported for the first time in a Turkish family. Additionally, it is suggested that the history of cardiac conduction problems such as cardiac arrest and sinus bradycardia might be related with mutant Cx30.

ABS TRACT De ter mi na ti on of the ori gin of the mar ker chro mo so mes is very dif fi cult and requires ef fort. Eva lu a ti on of the mar ker chro mo so mes of the preg nancy lost tis su e co uld be the most dif fi cult one as the con ta mi na ti on with ma ter nal de ci du al cells comp li ca tes this pro cess. Con ven ti o nal cyto ge ne tic tech ni qu es and flu o res cen ce in si tu hybri di za ti on tech ni qu e or mo re ad van ced mo le cu lar tech ni qu es are pre fer red to de ter mi ne the ori gin of the se chro mo so mes. In this re port, the study for iden ti fi ca ti on of the ori gin of an abor ti on ma te ri al de ri ved from the pri mary tis su e cell cul tu re, with a 47,XX,+mar(15) kar yoty pe was pre sen ted, by using an ef fec ti ve al go rith mic ap pro ach which en ded with ge noty ping. The re sult of the ge noty ping was in for ma ti ve, sin ce the as su med abor ti on ma te ri al ac tu ally be lon ged to the mot her’s de ci du al tis su e. This bri ef study re minds the ef fi ci ent al go rith mic ap pro ac hes to the de ter mi na ti on pro cess of the mar ker chro mo so mes of the abor ti on ma te ri al.

Monosomy 1p36 Syndrome is a well known, rare genetic disorder caused by the deletion in the distal part of the short arm of chromosome 1, in which prenatal and postnatal growth and mental retardation is usually accompanied by psychomotor retardation, late-closed large fontanels and typical fascial findings. Herein, a 16-year-old female subject considered to be Monosomy 1p36 Syndrome is presented. A deletion was determined in 1p36 region after high resolution banding (HRB) technique. This deletion determined with conventional cytogenetic analysis was confirmed using fluorescence in situ hybridization (FISH) technique [46,XX.ish del(1)(p36)dn]. This presentation emphasizes the importance of clinical diagnosis in Monosomy 1p36 Syndrome and the value of conventional methods and FISH technique in diagnosing this syndrome.

ObjectiveMitral valvar prolapse is the most common anomaly of the mitral valve apparatus throughout childhood. Fibrillin is one of the structural components of the elastin-associated microfibrils found in the mitral valve. A case-controlled study has performed to investigate the relationship between fibrillin 1 gene intron 56 polymorphism and risk of mitral valvar prolapse in Turkish children.Patients and methodsA total of 77 patients with mitral valvar prolapse diagnosed by clinical evaluation and echocardiography and 89 normal children of same age and sex were studied. The fibrillin-1 gene intron 56 polymorphism was identified by the polymerase chain reaction-based restriction analysis.ResultsThere was a significant difference in the distribution of fibrillin-1 gene intron 56 genotypes (p = 0.0001) and allelic frequency (p = 0.0001) between the cases and the controls.ConclusionsPatients with mitral valvar prolapse have higher frequencies of fibrillin-1 gene intron 56 GC genotypes. Healthy children have higher frequencies of fibrillin-1 gene intron 56 CC genotypes. We speculate that the higher frequency of fibrillin-1 gene intron 56 G-allele increases the risk of mitral valvar prolapse.

Aim: This study aimed to investigate the molecular testing of congenital hearing loss by using next generation sequencing technology. Pendred syndrome (PS) is described by severe bilateral sensorineural hearing loss with goiter. The mutations of SCL26A4 gene can cause PS. Material and Method: We evaluated the feasibility of target-enrichment and massive parallel sequencing technologies to interrogate all mutations of genes (GJB2, GJB3, GJB6, SLC26A4 and for the mitochondrial mutation A1555G) implicated in NSHL, we performed molecular analyses of 14 NSHL families and patients by using Miseq system (Illumina Inc.). Next-Generation sequencing (NGS) technologies provide specificity, sensitivity and reproducibility at levels sufficient to perform genetic diagnosis of hearing loss. Results: We found two different mutations in SCL26A4 gene such as F354S and I588T in both consanguineous families as diagnosed with Pendred syndrome and we reported a novel mutation in SCL26A4 gene. We found no mutation in GJB2, GJB3, GJB6 gene and A1555G mtDNA in this study. Conclusion: These results highlight the benefits using targeted gene panels with NGS technologies in the molecular analysis of nonsyndromic, congenital hearing loss patients. This study assessed the frequency of deafness genes in Turkish children with congenital hearing loss who had been treated with cochlear implantation, and we found a novel mutation (I588T) in SLC26A4 gene. Key Words: Pendred syndrome, Congenital Hearing Loss, Next-Generation sequencing

We report on a 2-year-old boy who was referred to our clinic with recurrent urinary tract infections, neurogenic bladder dysfunction and duplicated urethra. The child was unable to void spontaneously, and a suprapubic catheter had been placed. We performed an internal urethrotomy on his patent urethra, but the procedure did not successfully restore spontaneous voiding. After the surgery, we evaluated the child for the presence of congenital syndromes, especially the MURCS (Mullerian-Renal-Cervical Spine) association. Six months later, the patient underwent a left orchiopexy procedure. There was no evidence of the right testis. This case shows that the male variant of the MURCS association may accompany miscellaneous urogenital anomalies such as renal agenesis, cross renal ectopy, vesicoureteral reflux, neurogenic bladder dysfunction, posterior urethral valve, duplicated urethra, bilateral/unilateral undescended testes or vanishing testis.

Kılıç M, Şenel S, Karaer K, Ceylaner S. Microcephaly and developmental delay caused by short-chain acyl-CoA dehydrogenase deficiency. Turk J Pediatr 2017; 59: 708-710. We report a four-year-old girl who presented with intrauterine growth retardation, mild dysmorphism, cleft palate, microcephaly, developmental delay, epilepsy and recurrent lower respiratory tract infection and diagnosed short-chain acyl-CoA dehydrogenase deficiency. Metabolic evaluation and molecular analysis confirmed the diagnosis. In spite of many patients already known in literature, this is one of the rarest reports of a Turkish patient. This suggests selective metabolic screening should be done in every patient with unknown etiology of neurological disorder. Furthermore, newborn screening using tandem mass spectrometry may prevent this severe neurological impairment.

17-β-Hydroxysteroid dehydrogenase type 3 (17βHSD-3) is present almost exclusively in the testes, and converts androstenedione (A) to testosterone (T). 17βHSD-3 deficiency is rare. The diagnosis can be missed in early childhood as the clinical presentation may be subtle. The most frequent presentation of 17 HSD-3 deficiency is a 46,XY individual with female external genitalia, labial fusion and a blind ending vagina, with or without clitoromegaly. A low testosterone/androstenedion (T/A) ratio is suggestive of 17βHSD-3 deficiency, and such diagnosis can be confirmed with molecular genetic studies. A 12-day newborn was referred to our hospital because of palpable gonads in the labia majora. On physical examination, the baby had female external genitalia and palpable gonads in the labia majora. T/A ratio was 0.26 and the diagnosis was 17βHSD-3 deficiency, which was confirmed by the evidence of compound heterozygousity novel frameshift mutations in exon 9 and 10 of

Campomelic dysplasia (CD, OMIM #114290) is a rare autosomal dominant disease characterized with bending and shortness in the long bones of the lower extremities, typical facial features, hypoplastic scapula, costa defect, narrow thorax and pes equinovarus. Campomelic dysplasia occurs with heterozygous mutations in the SOX9 gene in the 17q24 chromosome. The main findings of our four-day old patient included typical facial features, risomelic extremity shortness, angular bending in the long bones of bilateral lower extremities and pes equinovarus. On direct graphies, costa defect and scapula hypoplasia were noted. We showed a missense mutation (c.473C>T [p.A158V]) in the SOX9 gene which had not been reported before in our patient who had the typical clinical findings of CD. The family of the patient was informed about potential future pathologies of this disease and received genetic counseling.

PubMedID: 28276217 Idiopathic generalized arterial calcification of infancy-1 (GACI-1) is a rare and potentially lethal disease characterized by diffuse calcification of large and medium-sized arteries such as aorta, renal, pulmonary, cerebral and mesenteric arteries. Here we report two new mutations in two newborn babies with GACI-1 treated with bisphosphonates, and their progress in the first year of life.

Pseudohypoparathyroidism (PHP) type Ia is characterized by multiple hormone resistance; primarily parathyroid hormone (PTH) resistance and Albright's hereditary osteodystrophy (AHO) which involves skeletal and developmental defects. The AHO phenotype alone without hormone resistance is defined as pseudoPHP. A boy was first diagnosed as having both rickets and primary hypothyroidism at 2.5 months of age. His calcium level remained within normal levels after vitamin D treatment, but, elevated PTH and ALP levels and normal-high phosphate levels persisted during his follow-up by age of 2.5 years. He was admitted with hypocalcemic convulsions as well as hyperphosphatemia and elevated PTH levels suggested PTH resistance at 2.5 years of age. He and his mother were obese and had round faces, frontal bossing, small noses, flat nasal bridges, brachydactyly. His mother showed no hormonal resistance. These findings indicated that our patient had PHP type Ia and his mother had pseudoPHP. The same novel heterozygous mutation in the GNAS gene (IVS4+5G > C) was identified in both of patients.

Gorlin-Chaudhry-Moss syndrome (OMIM 233500) is a rare congenital malformation syndrome with the cardinal manifestations of craniofacial dysostosis, hypertrichosis, underdeveloped genitalia, ocular, and dental anomalies. Since 1960, only six affected individuals have been reported. We report a 4-year and 6-month-old female patient with this phenotype and review the clinical presentation of all patients known so far. Previously unreported malformations of the extremities, larynx, and nose are also described, expanding the phenotype of this rare syndrome. Array-CGH analysis did not show pathological deletions or duplications.

Neurofibromatosis-Noonan syndrome is a rare autosomal dominant disorder which combines neurofibromatosis type 1 (NF1) features with Noonan syndrome. NF1 gene mutations are reported in the majority of these patients.Sequence analysis of the established genes for Noonan syndrome revealed no mutation; a heterozygous NF1 point mutation c.7549CT in exon 51, creating a premature stop codon (p.R2517X), had been demonstrated.Neurofibromatosis-Noonan syndrome recently has been considered a subtype of NF1 and caused by different NF1 mutations.We report the case of a 14-year-old boy with neurofibromatosis type 1 with Noonan-like features, who complained of headache with triventricular hydrocephaly and a heterozygous NF1 point mutation c.7549CT in exon 51.

The oto-spondylo-mega-epiphyseal-dysplasia (OSMED) phenotype is an autosomal recessive trait that is a skeletal dysplasia with the hallmark findings of limb shortening, multiple skeletal and radiological abnormalities, mid-face hypoplasia with a flat nasal bridge, small upturned nasal tip, and sensorineural hearing loss. A 3.5-year-old girl born to consanguineous Turkish parents had characteristic facial features at birth: mid-face hypoplasia, mild hypertelorism, upslanting palpebral fissures, prominent supraorbital ridges, depressed nasal bridge, small upturned nasal tip, long philtrum, and micrognathia. Radiological examination at three years of age revealed large flaring metaphyses and wide flat epiphyses. The humerus and femur showed the characteristic dumbbell shape. She had bilateral hearing loss with no ophthalmologic findings. There is continuing debate over the clinical overlap and differential diagnosis of OSMED syndrome. The patient was examined considering Weissenbacher-Zweymuller, Stickler type 3, Marshall syndrome, and Kniest dysplasia as possible differential diagnoses. We believe that the presented patient clinically manifested features of OSMED syndrome. We would like to point out that the management of OSMED calls for a coordinated multidisciplinary approach.

Ring chromosome 22, a rare cytogenetic finding, was first described in 1968, and since then about 60 patients have been reported. We describe a new patient with ring chromosome 22 syndrome and discuss the common features of the previously reported cases. Our patient had the major features of this syndrome including mental retardation, hypotonia, motor delay, microcephaly, dysplastic large ears, lack of speech, and hyperactivity disorder. Magnetic resonance imaging findings also revealed an arachnoid cyst, found in the posterior cerebellum. In patients with ring chromosome 22, variable clinical manifestations may be seen due to the size of lost sequences near the telomere. By fluorescent in situ hybridization (FISH) technique, LSI DiGeorge/VCFS/ ARSA locus-specific probes are used to detect deleted sequences. We found that 22q11.2 regions were intact on both chromosomes 22, but 22q13.3 (Arylsulfatase A; ARSA region) was absent in the ring chromosome. As far as we know this is the first reported Turkish patient in the literature.

Major neurological disorders may accompany rare chromosomal abnormalities. As an example of this rare condition, we present a case with microcephaly, mental retardation, developmental delay, hyperactivity, stereotypic movements, seizures and dysmorphic facial appearance in whom a mosaic ring chromosome 18 was found [45,XX,-18/46,XX,r(18)/46,XX,dicr(18)]. Although ring chromosome 18 phenotype has been known for a long time, this is the third reported patient with a dicentric ring chromosome 18 mosaicism. The presented case will contribute to the identification of the genotype-phenotype correlation in chromosome 18 anomalies.

The autism is a neurodevelopmental disorder of which the diagnosis depends on a ‘triad’ of deficits comprising impaired social interaction, impaired communication and restricted interests and repetitive behaviors. Hyperlexia is a syndrome observed in children who have the following characteristics: A precocious ability to read words, far above what would be expected at their chronological age or an intense fascination with letters or numbers, significant difficulty in understanding verbal language, abnormal social skills, and difficulty in socializing and interacting appropriately with people. In 1981, Niikawa and Kuroki described a group of patients who had characteristic facial features, skeletal anomalies, dermatoglyphic abnormalities, short stature, and mental retardation. Since, their facial features resembled the make-up actors in Kabuki, the traditional Japanese play, the term ‘Kabuki make-up syndrome’ was suggested (Niikawa and Matsuura 1981; Kuroki et al. 1981). Several patients with Kabuki Syndrome have been found to have autism or autistic-like behavior, with difficulties in both communication and peer interactions (Adam and Hudgins 2005; Ho and Eaves 1997). There exists no clinically available genetic test to confirm the diagnosis. However, five principal displays were defined; ‘Peculiar face’ in 100% of their patients, skeletal anomalies in 92% of their patients, dermatoglyphic abnormalities in 93% of their patients, mild to moderate mental retardation in 92% of their patients, postnatal growth deficiency in 83% of their patients (Adam and Hudgins 2005). In this report, there are some unreported situations for KS with autism, like the pregnancy is occurred by in-vitrofertilization, high-rated IQ and hyperlexia. Because of these situations is different in literature we would like to report and discuss this case.

This study was undertaken to determine the prevalence of Y-chromosome microdeletions in couples with recurrent pregnancy loss (RPL) as compared with fertile couples.Forty-three men from couples with recurrent pregnancy loss, and 43 men from couples with a live birth and no history of miscarriages were recruited from Zekai Tahir Burak Woman Health, Education and Research Hospital. The DNA was tested for the presence of 4 sequence tagged sites (STSs) spanning 4 AZF regions: DYS220 (AZFb), DYS235, DYS236, and DYS237 (AZFd).Seven (7) of the 43 men (16%) from couples with recurrent pregnancy loss had microdeletions in 1 or more of the 4 segments studied, whereas none of the fertile men had any microdeletions (P.05). Their microdeletions were all found specifically at locus DYS 220 (AZFb).The prevalence of the Y chromosome microdeletion in AZF region was much higher in men from couples with recurrent pregnancy loss than men in fertile couples. This study showed that Y chromosome microdeletion in AZF region may be a possible etiologic factor of recurrent pregnancy loss.

WOS: 000365765400011, PubMed ID: 26539891, Development of the human nervous system involves complex interactions among fundamental cellular processes and requires a multitude of genes, many of which remain to be associated with human disease. We applied whole exome sequencing to 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. Rare variant analyses for both single nucleotide variant (SNV) and copy number variant (CNV) alleles allowed for identification of 45 novel variants in 43 known disease genes, 41 candidate genes, and CNVs in 10 families, with an overall potential molecular cause identified in >85% of families studied. Among the candidate genes identified, we found PRUNE, VARS, and DHX37 in multiple families and homozygous loss-of-function variants in AGBL2, SLC18A2, SMARCA1, UBQLN1, and CPLX1. Neuroimaging and in silico analysis of functional and expression proximity between candidate and known disease genes allowed for further understanding of genetic networks underlying specific types of brain malformations., U.S. National Human Genome Research Institute (NHGRI) NHLBI grant [U54HG006542]; NINDSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [RO1 NS058529, K23NS078056]; NHGRIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [5U54HG003273]; Medical Genetics Research Fellowship Program [T32 GM07526]; Regeneron, We thank all the family members and collaborators who participated in this study. This work was supported by U.S. National Human Genome Research Institute (NHGRI) NHLBI grant U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics, NINDS grant RO1 NS058529 to J. R. L., and NHGRI 5U54HG003273 to R. A. G. T. H. is supported by the Medical Genetics Research Fellowship Program (T32 GM07526). W. W. is supported by Career Development Award K23NS078056 from NINDS. The authors would like to thank the ExAC and the groups that provided exome variant data for comparison. A full list of contributing groups can be found at http://exac.broadinstitute.org/about. J.R.L. has stock ownership in 23andMe and Lasergen and is a paid consultant for Regeneron. J. R. L. is also a coinventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from the chromosomal microarray analysis and clinical exome sequencing offered in the Medical Genetics Laboratory (https://www.bcm.edu/geneticlabs/). W. K. C. is a paid consultant for Regeneron and BioReference Laboratories. C.G.-J. and J. D. O. are employees of the RGC.