Mental Retardation, Autosomal Recessive 27

A number sign (#) is used with this entry because of evidence that autosomal recessive mental retardation-27 (MRT27) is caused by homozygous mutation in the LINS1 gene (610350) on chromosome 15q26.

Clinical Features

Najmabadi et al. (2011) reported a family (family 7903014) in which 4 of 6 children had moderate intellectual disability and microcephaly.

Akawi et al. (2013) reported 2 sibs, born of consanguineous parents of Yemeni descent, with autosomal recessive mental retardation. The patients had delayed psychomotor development with very poor or lack of speech, head nodding, mild flattening of the midface, hypotonia, and poor growth. They did not have microcephaly. Brain MRI of 1 patient showed right frontal lobe vascular malformation with cortical and subcortical distribution. Although neither patient had seizures, 1 had an abnormal EEG with bilateral centrotemporal discharges.

Mapping

By homozygosity mapping of a consanguineous Iranian family (8600086) in which 3 individuals had moderate nonsyndromic mental retardation, Kuss et al. (2011) found linkage to a locus on distal chromosome 15q. The candidate interval spanned 17.4 Mb between SNPs rs936227 and rs12906289 (lod score of 3.9).

By homozygosity mapping of a consanguineous Syrian family (MR068) in which 5 sibs had nonsyndromic mental retardation, Abou Jamra et al. (2011) found linkage to a 23.6-Mb region on distal chromosome 15q between SNPs rs868127 and rs2388310 (lod score of 3.38).

Molecular Genetics

Najmabadi et al. (2011) performed homozygosity mapping followed by exon enrichment and next-generation sequencing in 136 consanguineous families (over 90% Iranian and less than 10% Turkish or Arabic) segregating syndromic or nonsyndromic forms of autosomal recessive intellectual disability. In a family (family 7903014) in which 4 of 6 children had moderate intellectual disability and microcephaly, Najmabadi et al. (2011) identified a homozygous truncating mutation in the LINS1 gene (610350.0001).

In 2 sibs, born of consanguineous parents of Yemeni descent, with MRT27, Akawi et al. (2013) identified a homozygous 5-bp deletion in the LINS gene (610350.0002), resulting in a splicing defect. Analysis of patient cells showed that the mutation caused skipping of exon 5, which likely resulted in a truncated protein lacking several conserved amino acids, which was predicted to be deleterious to the function of the protein. The mutation was found by a combination of homozygosity mapping and whole-exome sequencing.