Case Report: Biallelic Variant in the tRNA Methyltransferase Domain of the AlkB Homolog 8 Causes Syndromic Intellectual Disability

• Published in: Frontiers in genetics 2022-04, Vol.13, p.878274
• Main Authors: Waqas, Ahmed, Nayab, Anam, Shaheen, Shabnam, Abbas, Safdar, Latif, Muhammad, Rafeeq, Misbahuddin M, Al-Dhuayan, Ibtesam S, Alqosaibi, Amany I, Alnamshan, Mashael M, Sain, Ziaullah M, Habib, Alaa Hamed, Alam, Qamre, Umair, Muhammad, Saqib, Muhammad Arif Nadeem
• Format: Article
• Language: English
• Subjects: biallelic variant; Genetics; intellectual disability; missense variant; posttranscriptional modification; tRNA methyl transferase; whole exome sequencing
• ISSN: 1664-8021; 1664-8021
• DOI: 10.3389/fgene.2022.878274

Intellectual disability (ID) has become very common and is an extremely heterogeneous disorder, where the patients face many challenges with deficits in intellectual functioning and adaptive behaviors. A single affected family revealed severe disease phenotypes such as ID, developmental delay, dysmorphic facial features, postaxial polydactyly type B, and speech impairment. DNA of a single affected individual was directly subjected to whole exome sequencing (WES), followed by Sanger sequencing. Data analysis revealed a novel biallelic missense variant (c.1511G>C; p.(Trp504Ser)) in the gene, which plays a significant role in tRNA modifications. Our finding adds another variant to the growing list of ALKBH8-associated tRNA modifications causing ID and additional phenotypic manifestations. The present study depicts the key role of the genes associated with tRNA modifications, such as , in the development and pathophysiology of the human brain.