A 15q13.3 homozygous microdeletion associated with a severe neurodevelopmental disorder suggests putative functions of the TRPM1, CHRNA7, and other homozygously deleted genes

Abstract

We identified a novel homozygous 15q13.3 microdeletion in a young boy with a complex neurodevelopmental disorder characterized by severe visual impairment, hypotonia, profound intellectual disability, and refractory epilepsy. The homozygous deletion of the genes within this deleted region provides a useful insight into the pathogenesis of the observed clinical phenotype. Absence of the Transient Receptor Potential Cation Channel, Subfamily M, Member 1 (TRPM1) gene product is proposed as a possible mechanism for the severe visual impairment; absence of CHRNA7 (alpha7-nicotinic receptor subunit) as a cause of the refractory seizures and severe cognitive impairment; and deletion of MTMR10 and/or MTMR15 (encoding myotubularin related proteins) alone or combined with other homozygously deleted genes as a cause for the congenital hypotonia with areflexia. The distinctive clinical findings in this patient reveal potential functions of the genes within the deleted region.