Edition of 23 March 2017

Three siblings presented with severe global developmental delay since birth, central hypotonia progressing to spastic quadraparesis, feeding difficulties, dystonia, prominent midline stereotypies, bruxism, high myopia, and epilepsy. Whole exome sequencing identified compound heterozygous variants in HTT that co-segregated in the three affected sibs and were absent in an unaffected sib.

The authors reported a unique neurometabolic human disorder caused by defective mitochondrial fatty acid synthesis. They proposed the name ‘MEPAN’ (mitochondrial enoyl CoA reductase protein-associated neurodegeneration) for this disorder. Seven individuals from five unrelated families presented with childhood-onset dystonia, optic atrophy, and basal ganglia signal abnormalities on MRI. All affected individuals were found to harbour recessive mutations in MECR.

The authors described three unrelated families affected by a previously unclassified form of anterior segment dysgenesis. Shared ocular manifestations included bilateral iris hypoplasia, ectopia lentis, corectopia, ectropion uveae, and cataracts. Whole-exome sequencing and targeted Sanger sequencing identified mutations in CPAMD8 as the cause of recessive anterior segment dysgenesis in all three families.

Whole exome sequencing was performed in patients with osteogenesis imperfecta. It identified compound heterozygous variants in NBAS in two patients with a multi-system phenotype. The first patient was a 10-year old boy with significant short stature, bone fragility requiring treatment with bisphosphonates, developmental delay and immunodeficiency. The second patient was a 5-year old boy with similar presenting features, bone fragility, mild developmental delay, abnormal liver function tests and immunodeficiency.

The authors characterised a novel class of congenital myopathy. They described a cohort of 11 patients from 7 families presenting with perinatal hypotonia, severe axial and generalised weakness. Ophthalmoplegia was present in four patients. Exome sequencing revealed recessive and dominant mutations in CACNA1S.

The authors evaluated a 45-year-old woman showing symptoms of combined immunodeficiency with severe bacterial and herpetic infections, and disturbed glucose metabolism since birth with hypoglycemia. They performed whole-exome sequencing and identified novel compound heterozygous missense mutations in HYOU1.