Maternal uniparental isodisomy and heterodisomy on chromosome 6 encompassing a CUL 7 gene mutation causing 3M syndrome

Sasaki K, Okamoto N, Kosaki K, Yorifuji T, Shimokawa O, Mishima H, Yoshiura K‐i, Harada N. Maternal uniparental isodisomy and heterodisomy on chromosome 6 encompassing a CUL 7 gene mutation causing 3M syndrome. We report a case of segmental uniparental maternal hetero‐ and isodisomy involving the whole of chromosome 6 (mat‐hUPD6 and mat‐iUPD6) and a cullin 7 ( CUL7 ) gene mutation in a Japanese patient with 3M syndrome. 3M syndrome is a rare autosomal recessive disorder characterized by severe pre‐ and postnatal growth retardation that was recently reported to involve mutations in the CUL7 or obscurin‐like 1 ( OBSL1 ) genes. We encountered a patient with severe growth retardation, an inverted triangular gloomy face, an inverted triangle‐shaped head, slender long bones, inguinal hernia, hydrocele testis, mild ventricular enlargement, and mild mental retardation. Sequence analysis of the CUL7 gene of the patient revealed a homozygous missense mutation, c.2975G>C. Genotype analysis using a single nucleotide polymorphism array revealed two mat‐hUPD and two mat‐iUPD regions involving the whole of chromosome 6 and encompassing CUL7 . 3M syndrome caused by complete paternal iUPD of chromosome 6 involving a CUL7 mutation has been reported, but there have been no reports describing 3M syndrome with maternal UPD of chromosome 6. Our results represent a combination of iUPDs and hUPDs from maternal chromosome 6 involving a CUL7 mutation causing 3M syndrome.