FIG4-Associated Yunis-Varon Syndrome: Identification of a Novel Missense Variant

Abstract

Yunis-Varon syndrome (YVS; OMIM 216340) is a rare heterogeneous autosomal recessive disorder with easy recognition of characteristic severe neurological and skeletal abnormalities involving skeletal muscles and cartilages. This cleidocranial dysplasia is characterized by bone and tooth disorders; it also affects the cardiovascular system and tissues from ectoderm with very poor outcomes. Rarely, mutations of the <i>FIG4</i> gene, encoding a 50-phosphoinositide phosphatase have been identified as the cause for YVS. We report a neonate born to a consanguineous couple with typical clinical manifestations of YVS. Using whole-exome sequencing, we identified a novel homozygous missense variant (c.968A&#x3e;G; p.Gln323Arg) in the <i>FIG4</i> gene. Thus, our study expands the molecular and genetic spectrum of <i>FIG4</i>-associated mutations. To our knowledge, this is the first reported case of YVS from the Saudi population.