Molecular Characteristics
The ADAT3 (Adenosine Deaminase, tRNA-Specific, 3) gene is located at 19p13.3 and encodes a 322-residue protein necessary for the deamination of adenosine at position 34 to inosine in t-RNA.
Mutations and pathophysiology
Alazami et al. (2013) reported a homozygous missense mutation in the ADAT3 gene (NM_138422: c.382G>A, p.V128M) in 24 individuals from 8 consanguineous families. Molecular studies revealed that the mutation induces a kink that disrupts the protrusion on the surface of the protein. Intellectual disability and esotropia were the most consistent clinical findings; microcephaly, hypotonia, failure to thrive, and abnormal brain structure were also frequently seen.
El-Hattab et al. (2016) reported homozygosity for the same c.382G>A mutation in 15 individuals from 11 consanguineous families. The clinical features were similar to those reported by Alazami et al. (2013)
Recently, Salehi Chaleshtori et al. (2015) identified homozygosity for an 8-bp duplication (c.99_106dupGAGCCCGG, p.(Glu36Glyfs*44)) in a 6-year-old Iranian girl born to a consanguineous family and presenting with intellectual disability, microcephaly, and hyperactivity.