ClinVar

In affected members of 8 consanguineous Arab families with neurodevelopmental disorder with brain abnormalities, poor growth, and dysmorphic facies (NEDBGF; 615286) Alazami et al. (2013) identified a homozygous c.382G-A transition in the ADAT3 gene, resulting in a val128-to-met (V128M) substitution at a highly conserved residue. Molecular modeling indicated that the mutation occurs in a hook that protrudes from the surface of the protein and would disrupt this protrusion. The mutation, which was found by homozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in all families and was not found in several large control exome databases or in 580 ethnically matched alleles. Haplotype analysis indicated a founder effect, which was estimated to have occurred between 65 and 111 generations ago. Most of the patients also had esotropia and failure to thrive; some had microcephaly and mild brain malformations on MRI.

In 15 affected members of 11 apparently unrelated Arab families with NEDBGF, El-Hattab et al. (2016) identified homozygosity for the same V128M founder mutation in the ADAT3 gene. El-Hattab et al. (2016) noted that all but 1 of the families with this mutation were from Saudi Arabia.

Sharkia et al. (2019) identified a homozygous V128M mutation in 2 sibs, born of consanguineous Arab parents, with NEDBGF. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed.