Two New Families With TAF13 Variant Presenting With Syndromic 46,XY Disorder of Sex Development: Expanding the Clinical Phenotype.

Abstract

Intellectual developmental disorder, autosomal recessive 60 (MRT60, #617432) is an ultrarare genetic disorder characterized by microcephaly, intellectual disability, growth retardation, seizure, and central nervous system abnormalities. The disease is caused by biallelic variants in the TATA box-binding protein-associated factor gene (TAF13) gene. To date, only four patients with MRT60 have been reported in the literature. In this study, two new patients were presented, exhibiting similar phenotypic features including microcephaly, intellectual disability, and prominent growth retardation. Whole exome analysis revealed a pathogenic variant (c.119T>A p.Met40Lys) in the TAF13 gene. The 46,XY disorder of sex development was only present in the current patients and is a new finding for this ultrarare disorder. Since TAF13 plays a role in transcriptional regulation, it is believed to potentially cause gonadal dysfunction. To obtain a better understanding of this disorder, it is essential to conduct comprehensive functional studies that can provide deeper insights into the underlying mechanisms.