A novel recessive mutation in the gene ELOVL4 causes a neuro-ichthyotic disorder with variable expressivity.

BACKGROUND: A rare neuro-ichthyotic disorder characterized by ichthyosis, spastic quadriplegia and intellectual disability and caused by recessive mutations in ELOVL4, encoding elongase-4 protein has recently been described. The objective of the study was to search for sequence variants in the gene ELOVL4 in three affected individuals of a consanguineous Pakistani family exhibiting features of neuro-ichthyotic disorder. METHODS: Linkage in the family was searched by genotyping microsatellite markers linked to the gene ELOVL4, mapped at chromosome 6p14.1. Exons and splice junction sites of the gene ELOVL4 were polymerase chain reaction amplified and sequenced in an automated DNA sequencer. RESULTS: DNA sequence analysis revealed a novel homozygous nonsense mutation (c.78C > G; p.Tyr26*). CONCLUSIONS: Our report further confirms the recently described ELOVL4-related neuro-ichthyosis and shows that the neurological phenotype can be absent in some individuals.

A novel WDR62 mutation causes primary microcephaly in a Pakistani family.

Autosomal recessive primary microcephaly (MCPH) is a heterogeneous disorder which mainly affects neurodevelopment. Generally, MCPH patients exhibit mild brain structural anomalies and simplified cerebral cortex, but few recently identified genes are associated with severe brain malformations. Here, we report a five generation Pakistani family with three affected individuals presenting primary microcephaly, intellectual disability, schizencephaly and hypoplasia of corpus callosum. The comparison of available clinical information led to candidate gene mapping and sequencing of WD repeat domain 62 (WDR62) gene which is mostly associated with severe brain malformations. A homozygous deletion mutation c.1143delA was detected in exon 9 of WDR62 gene, in all affected individuals, which resulted in frameshift and protein truncation (p.H381PfsX48). This study supports the frequent involvement of WDR62 in patients with gross brain malformations.