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en Genetic Screening of Iranian Patients with 46,XY Disorders of Sex Development تخصصي Special مقالات اصلی Original Article Background: Disorders of sex development (DSDs) belong to uncommon pathologies and result from abnormalities during gonadal determination and differentiation. Various gene mutations involved in gonadal determination and differentiation have been associated with gonadal dysgenesis. Despite advances in exploration of genes and mechanisms involved in sex disorders, most children with severe 46,XY DSDs have no definitive etiological diagnoses; therefore, the possibility that other genes or loci might play important roles in these disorders needs to be explored. Methods: Patients (37) clinically suspicious for 46,XY gonadal dysgenesis (46,XY GD) of unknown etiology were studied. SRY, encoding the sex-determining region Y protein, NR5A1, encoding a transcription factor called steroidogenic factor 1, and DHH, encoding the desert hedgehog protein, were directly sequenced. Multiplex ligation-dependent probe amplification (MLPA) was used to detect deletions in NR0B1, encoding the DAX1 protein, and WNT4, encoding the WNT4 protein, and real-time PCR (qPCR) confirmed the MLPA data. Other potential loci have been investigated in the complete genome using Array-Comparative Genomic Hybridization, (Array CGH). Results: The SRY deletion was found in five patients. One each of previously described NR5A1, DHH, and AR (androgen receptor) allelic variants were identified. A pathogenic c.2522G>A AR mutation was found in two affected brothers. A heterozygous partial deletion was found in NR5A1 and heterozygous partial duplications were found in WNT4. These deletions and duplications (del/dup) were confirmed by qPCR. The Array CGH result demonstrated one partial deletion in SOX2-OT, which encodes a member of the SOX family of transcription factors, and the exact region of the rearrangements. Conclusions: According to our study, del/dup mutations could be checked prior to point mutations, SOX2-OT has a potential role in gonadal dysgenesis, and Array CGH has a prominent role in gonadal dysgenesis diagnosis. Array-Comparative Genomic Hybridization, (Array-CGH), Disorders of sex development (DSDs), Mutation 59 65 http://rbmb.net/browse.php?a_code=A-10-1-83&slc_lang=en&sid=1 Azadeh Shojaei 10031947532846005559 10031947532846005559 Yes Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. Reza Ebrahimzadeh-Vesal 10031947532846005560 10031947532846005560 No Department of Basic Medical Science, Faculty of Medicine, Neyshabur University of Medical Sciences, Neyshabur, Iran. Ali Ahani 10031947532846005561 10031947532846005561 No Mendel medical genetic laboratory, Tehran, Iran Maryam Razzaghy-Azar 10031947532846005562 10031947532846005562 No : Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Iran University of Medical Sciences, Tehran, Iran; H. Aliasghar Hospital, Iran University of Medical Sciences, Tehran, Iran. Golnaz khakpour 10031947532846005563 10031947532846005563 No Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Farideh Ghazi ghazi.f@iums.ac.ir 10031947532846005564 10031947532846005564 No Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. Javad Tavakkoly-Bazzaz tavakkolybazzazj@tums.ac.ir 10031947532846005565 10031947532846005565 No Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.