A novel c.2T > C mutation of the KDM5C/JARID1C gene in one large family with X-linked intellectual disability.
Mutations in the KDM5C gene (lysine (K)-specific demethylase 5C gene; also known as JARID1C and SMCX; MIM 314690) were recently associated with X-linked intellectual disability (XLID). To date only two case reports and five studies that screen for mutations in the KDM5C gene have been published, with 21 mutations reported. Herein we present a large family with XLID caused by a novel mutation c.2T > C in the start codon of the KDM5C gene, presumably leading to loss of gene translation. Six sibs out of seven (two sons and four sisters) and their mother carry this mutation. Two affected males presented the distinctive clinical phenotype, characterized by moderate short stature, clumsy gait, ataxia, increased muscle tone and brisk tendon reflexes. They constantly bore a happy and smiling facial expression, with a protruding tongue. We hereby offer the first thorough description of five affected females with the KDM5C gene mutation. Most frequent clinical features were short stature, facial dysmorphism and developmental problems. X-chromosome inactivation study showed completely skewed inactivation pattern of mutation-carrying chromosome in all affected female patients.
Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia. katrin.ounap@kliinikum.ee
Katrin
K
Ounap
Helen
H
Puusepp-Benazzouz
Maire
M
Peters
Ulvi
U
Vaher
Reet
R
Rein
Anne
A
Proos
Mike
M
Field
Tiia
T
Reimand
D000293:Adolescent; D000328:Adult; D002648:Child; D005190:Family; D005260:Female; D056466:Histone Demethylases; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D009154:Mutation; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D055815:Young Adult
D056466:Histone Demethylases; C086877:KDM5C protein, human; D010089:Oxidoreductases, N-Demethylating