DefinePK

Abstract

ABSTRACT The THOC6 protein is a component of the THO complex, which plays a role in transcription, mRNA processing, and export from the nucleus. Homozygous loss-of-function variants in the THOC6 gene have been first identified in patients with Beaulieu-Boycott-Innes syndrome (BBIS). To date, 24 cases of THOC6-related BBIS from 18 families have been reported in 15 studies across various populations. In this study, we aimed to investigate the genetic basis of intellectual disability in a consanguineous family from Pakistan. The family had three siblings with intellectual disability, and whole exome sequencing was performed to identify pathogenic variants which were later validated through Sanger sequencing. This study was conducted at the Centre of Excellence in Molecular Biology, University of the Punjab, Lahore. We identified a novel homozygous missense mutation (c.508T>C; p.Tyr170His) in the THOC6 gene in all three affected siblings of PKMR427. The mutation was found to segregate in the family along with the phenotype, and clinical assessment confirmed the typical features of BBIS. This is the first report of a THOC6 gene mutation from Pakistan, and it substantiates the candidacy of THOC6 as a gene involved in BBIS. It also expands the study spectrum of this syndrome.