Edition of 06 June 2017

The authors reported biallelic pathogenic variants in OTUD6B in 12 individuals from 6 independent families with an intellectual disability syndrome associated with seizures and dysmorphic features. In subjects with predicted loss-of-function alleles, additional features included global developmental delay, microcephaly, absent speech, hypotonia, growth retardation with prenatal onset, feeding difficulties, structural brain abnormalities, congenital malformations including congenital heart disease, and musculoskeletal features.

The authors investigated four individuals from a single consanguineous Omani family aged between 19 months and 15 years that presented with a novel autosomal recessive complicated form of hereditary spastic paraplegia with brain white matter involvement. That disorder was associated with a mutation in EPT1, responsible for the final step in Kennedy pathway forming phosphatidylethanolamine from CDP-ethanolamine.

A novel autosomal recessive cerebro-renal syndrome was identified in consanguineous Bedouin kindred: neurological deterioration was evident as of early age, progressing into severe intellectual disability, profound ataxia, camptocormia and oculomotor apraxia. Brain MRI was normal. Four of the six affected individuals also had early-onset nephropathy with features of tubulo-interstitial nephritis, hypertension and tendency for hyperkalemia, though none had rapid deterioration of renal function. Whole exome sequencing identified a single mutation in SLC30A9 segregating within the kindred and not found in a homozygous state in 300 Bedouin controls.

The authors employed whole-exome sequencing in two unrelated consanguineous kindreds with central nervous system, cardiac, renal, and digit abnormalities. They identified homozygous truncating mutations in TMEM260.