A novel missense heterozygous mutation in MAP3K1 gene causes 46, XY disorder of sex development: case report and literature review.

Aisha Al Shamsi, Noura Al Hassani, Moustafa Hamchou, Raya Almazrouei, Aziz Mhanni

Molecular genetics & genomic medicine 2020 Nov

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Disorders of sex development (DSD) can result from congenital defect in sex determining pathway. Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is one of the commonest genes that has been identified to cause 46, XY DSD. It can present as complete or partial gonadal dysgenesis even within the same kindred. Few mutations in this gene have previously been identified in a high proportion of individuals with 46, XY gonadal dysgenesis. We report three siblings with same novel variant in MAP3K1 gene presenting with variable degrees of partial gonadal dysgenesis. Clinical and genetic assessments were performed for the three siblings, while endocrine evaluation was done for two of them. The identified mutation (p.Thr657Arg) was previously classified as a pathogenic variant, although apparently there are no reported humans with this mutation. This report adds to the genotype-phenotype correlation, highlighting the clinical importance of considering MAP3K1 gene defects as part of the differential diagnosis for complete or partial gonadal dysgenesis especially with multiple affected family members. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.

Citation

Aisha Al Shamsi, Noura Al Hassani, Moustafa Hamchou, Raya Almazrouei, Aziz Mhanni. A novel missense heterozygous mutation in MAP3K1 gene causes 46, XY disorder of sex development: case report and literature review. Molecular genetics & genomic medicine. 2020 Nov;8(11):e1514