Edition of 28 June 2019

A new study published in the American Journal of Human Genetics recently identified five individuals from three pedigrees with phenotypes including intellectual disability, behavioral difficulties, and dysmorphic features who were found via whole exome sequencing to have variants in BCORL1. BCORL1, a transcriptional corepressor, is involved in negative gene regulation through associations with several protein complexes including Class II histone deacetylases (HDACs). Hemizygous pathogenic variants in BCORL1 may underlie a newly identified X-linked epigenetic syndrome.

A recent study published in the PLOS Genetics identified homozygous loss-of-function mutations in PIK3C2A in children from three independent consanguineous families with short stature, coarse facial features, cataracts with secondary glaucoma, multiple skeletal abnormalities, neurological manifestations. These features were due to deficiency of the PIK3C2A enzyme, playing a critical role in growth, vision, skeletal formation and neurological development. This syndrome is the first monogenic disorder caused by mutations in a class II PI3K family member.

The American Journal of Human Genetics recently published a study describing the presentation of pathogenic mutations in a catalytic component of a B family DNA polymerase member, DNA polymerase α. By using various complementary approaches, including classical linkage analysis, targeted next-generation sequencing, and whole-exome sequencing, the study describes distinct missense and splice-impacting mutations in POLA1, encoding the p180 catalytic subunit of DNA polymerase α-primase, in five unrelated families presenting with an X-linked syndrome involving intellectual disability, proportionate short stature, microcephaly, and hypogonadism.