ClinVar

In a brother and sister, born of first-cousin Moroccan parents, with microcephaly, short stature, and polymicrogyria (MSSP; 614833), Grandone et al. (2016) identified a homozygous T-to-C transition (chr18.6,780,1710T-C, GRCh37) at the penultimate base of exon 23 of the RTTN gene, resulting in an arg985-to-gly (R985G) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the gnomAD database. Grandone et al. (2016) showed that the mutation also led to a splicing abnormality, resulting in 2 different mRNAs, one that skipped exon 23, and the other that skipped exons 23 and 24, producing an out-of-frame messenger.

In a boy, born of consanguineous Moroccan parents, with MSSP, Cavallin et al. (2018) identified homozygosity for the R985G mutation in the RTTN gene. The mutation, which was found by trio-based whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family.