Edition of 18 September 2019

A study published in the European Journal of Medical Genetics identified two siblings with delayed psychomotor development, absent speech, severe intellectual disability and postnatal microcephaly, with brain malformations consisting of cerebellar atrophy in the eldest affected and hypoplastic corpus callosum in the younger sister. Whole exome sequencing revealed a homozygous intragenic deletion in VPS51, which encodes the vacuolar protein sorting-associated protein, one the four subunits of the Golgi-associated retrograde protein and endosome-associated recycling protein complexes that promotes the fusion of endosome-derived vesicles with the trans-Golgi network and recycling endosomes. It confirmed the key role of membrane trafficking in normal brain development and homeostasis.

A new study published in Genetics in Medicine reported 16 newly identified individuals with heterozygous USP7 variants, identified by genome or exome sequencing or by chromosome microarray analysis. Clinical features were evaluated by review of medical records. Additional clinical information was obtained on seven previously reported individuals to fully elucidate the phenotypic expression associated with USP7 haploinsufficiency. The clinical manifestations of these 23 individuals suggest a syndrome characterized by developmental delay/intellectual disability, hypotonia, eye anomalies, feeding difficulties, gastroesophageal reflux disease, behavioral anomalies, and autism spectrum disorder, and more specific phenotypes of speech delays including a nonverbal phenotype and abnormal brain magnetic resonance image findings including white matter changes based on neuroradiologic examination.

A new study published in the American Journal of Human Genetics reported two homozygous missense mutations (c.209T>A [p.Ile70Lys] and c.1149C>A [p.Asn383Lys]) in five individuals from three unrelated families. All individuals presented with global developmental delay, severe-to-profound intellectual disability, muscular hypotonia, seizures, brain anomalies, scoliosis, and mild facial dysmorphism. This study improved the understanding of the role of the GPI transamidase complex in the development of nervous and skeletal systems and expand the clinical spectrum of disorders belonging to the group of inherited GPI-anchor deficiencies.