Edition of 04 February 2017

The authors reported five individuals with de novo missense substitutions in CHD4 identified through whole-exome sequencing and web-based gene matching. These individuals had overlapping phenotypes including developmental delay, intellectual disability, hearing loss, macrocephaly, distinct facial dysmorphism, palatal abnormalities, ventriculomegaly, and hypogonadism as well as additional findings such as bone fusions.

Exome sequencing revealed pathogenic biallelic mutations in NAXE in children from four families with (sub-) acute-onset ataxia, cerebellar oedema, spinal myelopathy, and skin lesions. Lactate was elevated in cerebrospinal fluid of all affected individuals. Disease onset was during the second year of life and clinical signs as well as episodes of deterioration were triggered by febrile infections. Disease course was rapidly progressive, leading to coma, global brain atrophy, and finally to death in all affected individuals.

The authors identified a recurrent de novo ATAD3A variant by whole-exome sequencing in five unrelated individuals with a core phenotype of global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy. They also described two families with biallelic variants in ATAD3A, including a homozygous variant in two siblings, and biallelic ATAD3A.

Whole exome sequencing was performed on four unrelated probands with left ventricular non-compaction, developmental delay, seizures, and severe hypotonia. Biallelic single nucleotide variants or copy number variants in MIPEP were present in all four probands, three of whom had infantile/childhood death.