Cerebellar hypoplasia with endosteal sclerosis is a POLR3-related disorder

• DOI: 10.1038/ejhg.2017.73
• Publication Date: 2017-06-07T10:20:46Z
• Authors: Jamal Ghoumid; Florence Petit; Odile Boute-Benejean; Frédéric Frenois; Maryse Cartigny; Clémence Vanlerbe...; Thomas Smol; Roseline Caumes; Nicolas de ROUX; Sylvie Manouvrier...
• Keywords: Male; 0301 basic medicine; Heterozygote; 03 medical and health sciences; Adolescent; Cerebellar Ataxia; [SDV]Life Sciences [q-bio]; Mutation, Missense; Humans; RNA Polymerase III; Osteosclerosis

CHES (cerebellar hypoplasia with endosteal sclerosis) syndrome (OMIM#213002) associates hypomyelination, cerebellar atrophy, hypogonadism and hypodontia. So far, only five patients have been described. The condition is of neonatal onset. Patients have severe psychomotor delay and moderate to severe intellectual disability. Inheritance is assumed to be autosomal recessive due to recurrence in sibs, consanguinity of parents and absence of vertical transmission. CHES syndrome is reminiscent of 4H-leukodystrophy, a recessive-inherited affection due to variations in genes encoding subunits of the RNA polymerase III (POLR3A-POLR3B-POLR1C). POLR3B variants have been identified in one CHES patient. Here we report on a novel CHES patient, carrying compound heterozygous variations in POLR3B. This report confirms affiliation of CHES to POLR3-related disorders and suggests that CHES syndrome represents a severe form of 4H-leukodystrophy.