A novel mutation of WDR62 gene associated with severe phenotype including infantile spasm, microcephaly, and intellectual disability

6533b82dfe1ef96bd1291dcf

RESEARCH PRODUCT

A novel mutation of WDR62 gene associated with severe phenotype including infantile spasm, microcephaly, and intellectual disability

Salvatore Mangano Antonina Fontana Rosaria Nardello Giuseppe Donato Mangano Maria Cristina Stallone Annalisa Beninati Vincenzo Antona

subject

Male 0301 basic medicine Microcephaly Adolescent Mutation Missense Intellectual disability Cell Cycle Proteins Nerve Tissue Proteins Genetic analysis Receptors G-Protein-Coupled Consanguinity 03 medical and health sciences 0302 clinical medicine Developmental Neuroscience Settore M-PSI/08 - Psicologia Clinica Intellectual disability Humans Medicine Missense mutation Gene WDR62 Genetics MCPH Epilepsy business.industry Genetic heterogeneity Infant General Medicine Infantile Spasm medicine.disease Settore MED/39 - Neuropsichiatria Infantile Pedigree Phenotype 030104 developmental biology GPR56 Mutation Pediatrics Perinatology and Child Health Microcephaly Infantile spasm Neurology (clinical)business Spasms Infantile 030217 neurology & neurosurgery

description

Abstract The autosomal recessive form of primary microcephaly (MCPH) is a rare disorder characterized by head circumference of at least 3 standard deviation below the mean. The MCPH exhibits genetic heterogeneity with thirteen loci (MCPH1-MCPH13) identified, and associated with variable degree of intellectual disability. It has been reported that WDR62 is the second causative gene of autosomal recessive microcephaly (MCPH2) playing a significant role in spindle formation and the proliferation of neuronal progenitor cells. We report a clinical feature, electroclinical findings, and clinical course of a patient with a severe phenotype of MCPH2 including microcephaly, refractory infantile spasms and intellectual disability. Genetic analysis detected a new homozygous splicing variant c.3335+1G>C in the WD repeat domain 62 ( WDR62 ) gene, inherited from both heterozygous healthy parents, and an additional new heterozygous missense mutation c.1706T>A of G protein-coupled receptor 56 ( GPR56 ) gene inherited from his healthy father. The study seeks to broaden the knowledge of clinical and electroclinical findings of MCPH2 and to contribute to a better characterization of the genotype-phenotype correlation.

year	journal	country	edition	language
2017-02-16	Brain and Development

https://doi.org/10.1016/j.braindev.2017.07.003