A Rare Cause of Intellectual Disability: Novel Mutation of ALKBH8 Gene in Two Different Families and Review of the Literature

ABSTRACT

The ALKBH8 gene encodes the ABH8 protein, which is responsible for modifying tRNAs by methylating the anticodon wobble uridine residues. Variations in the ALKBH8 gene are associated with the phenotype “intellectual developmental disorder, autosomal recessive type 71” (MRT71). To date, 14 patients from six different families carrying variants in the ALKBH8 gene have been reported in the literature. In the present study, we report four patients exhibiting clinical features of intellectual disability and dysmorphic facial features from two unrelated Turkish families who harbored a novel homozygous frameshift variant in the ALKBH8 gene. Whole‐exome sequencing of the index patients identified a novel homozygous frameshift variant in the ALKBH8 gene, NM_138775.3:c.1333_1334del (p.Arg445Alafs*8), which was classified as likely pathogenic according to American College of Medical Genetics and Genomics (ACMG) criteria. In this case study, we aimed to describe two unrelated Turkish families with an ultra‐rare disease associated with mutations in the ALKBH8 gene. Furthermore, we sought to identify a novel variant and characterize the associated clinical findings to contribute to a refined understanding of the phenotypic and genotypic spectrum of this syndrome.