Edition of 18 January 2022

A new study published in the American Journal of Human Genetics identified biallelic deleterious variants in the gene coding for ABHD16A (a phospholipase), within 11 individuals (from six unrelated families) who express a complicated form of HSP, with a similar phenotype consisting of global developmental delay/intellectual disability, progressive spasticity affecting the upper and lower limbs, and corpus callosum and white matter anomalies. Immunoblot analysis on extracts from fibroblasts from four affected individuals demonstrated little to no ABHD16A protein levels compared to controls. These findings add ABHD16A to the growing list of lipid genes in which dysregulation can cause complicated forms of HSP and begin to describe the molecular etiology of this condition.

A new study published in Genetics in Medicine identified seven missense variants in the gene coding for UBA2 (ubiquitin-like modifier-activating enzyme 2), among some of the 16 individuals tested (from 7 unrelated families). The later express ACC, ectrodactyly, neurodevelopmental abnormalities, ectodermal, skeletal, craniofacial, cardiac, renal, and genital anomalies. A fish model (knockdown, and rescue experiments) suggest a causality, and highlights the importance of SUMOylation in the development of affected tissues.