Identification of mutations in Iranian patients’ DAX-1 gene with X-linked adrenal hypoplasia congenital

Davoodnejad, M. and Eshraghi, P. and vakili, R. and Hamzehloie, T. (2017) Identification of mutations in Iranian patients’ DAX-1 gene with X-linked adrenal hypoplasia congenital. Egyptian Journal of Medical Human Genetics, 18 (2). pp. 165-172.

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Abstract

Objective(s) X-linked adrenal hypoplasia congenital (X-linked AHC) is a rare disorder, characterized by infantile-onset acute primary adrenal insufficiency and hypogonadotropic hypogonadism (HH) at an average age of three weeks and onset in roughly 40 is in childhood. Its cause is an inactivating mutation in the (nuclear receptor subfamily 0, group B, member 1) NR0B1 gene, DSS (dosage sensitive sex)-AHC vital region on the X-gene 1. Subjects and methods In the present study, the (dosage-sensitive, sex reversal, adrenal hypoplasia congenital, important region on the X-chromosome, gene 1) DAX-1 gene from four Iranian patients with X-linked AHC was analyzed by means of polymerase chain reaction (PCR) and direct sequencing. Results We identified a polymorphism (Rs6150) which encodes a cysteine (Cys) at position 38, a de novo deletion, c.849-928del79 bp, c.849-856ins, (TGCTGCA) mutation and a missense mutation, Leu262Gln, which encodes a leucine (Leu) for glutamine (Gln) at position 262. Conclusion Both mentioned mutations are located at crucial and functional region DAX1 protein. They are detected in the C-terminal region of DAX1 protein which is involved by the conserved amino acid chain as well as transcriptional silencing domain. By considering other investigation, mutations in this region probably lead to produce a misfolded protein. Consequently, the misfolded protein would not work influentially in order to inhibit some gene expression. As a result, our findings will expand the variety of DAX1 mutations. On the other hand, it is revealed that these mutations play a key role in the pathogenesis of AHC, thus, recognizing these new mutations will facilitate the patients prognosis producer as well as raising the clinical knowledge about this rare disease. © 2016 Ain Shams University

Item Type: Article
Additional Information: Export Date: 16 February 2020 Correspondence Address: Hamzehloie, T.; Department of Human Genetic, School of Medicine, Mashhad University of Medical SciencesIran
Uncontrolled Keywords: DAX1 protein NR0B1 gene X-linked adrenal hypoplasia congenital (X-linked AHC) cysteine glutamine leucine nuclear receptor DAX 1 adrenal gland malformation Article case report child congenital adrenal hypoplasia gene deletion gene mutation genetic polymorphism human infant Iranian (citizen) male missense mutation molecular pathology polymerase chain reaction preschool child sequence analysis X chromosome linked disorder
Subjects: WK Endocrine System
QU Biochemistry
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib3 lib3
Date Deposited: 13 May 2020 05:37
Last Modified: 13 May 2020 05:37
URI: http://eprints.mums.ac.ir/id/eprint/16795

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