Edition of 22 October 2019

A new study recently published in Genetics in Medicine identified five unrelated families with a distinct autosomal dominant ocular systemic disorder we called ROSAH syndrome due to clinical features of retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache. The heterozygous missense variant in the ɑ-kinase gene, ALPK1, segregated with disease in all five families was identified. All patients shared the ROSAH phenotype with additional low-grade ocular inflammation, pancytopenia, recurrent infections, and mild renal impairment in some. Heterozygosity for ALPK1 leads to ROSAH syndrome, an autosomal dominant ocular systemic disorder. Heterozygosity for ALPK1 leads to ROSAH syndrome, an autosomal dominant ocular systemic disorder.

A study published in Brain identified 10 individuals from six unrelated families, exhibiting a neurodevelopmental disorder characterized with a spectrum of central (intellectual disability, developmental delay, motor impairment, speech difficulties) and peripheral (early onset demyelinating neuropathy) neurological involvement, who were found by exome or genome sequencing to carry one frameshift and four different homozygous non-synonymous variants in NFASC. The assembly of myelinated fibres and nodes of Ranvier is mediated by a number of cell adhesion molecules of the immunoglobulin superfamily including neurofascin, encoded by the NFASC gene. This study highlighter the importance of this gene in human brain development and function.