Novel JARID1C/SMCX mutations in patients with X-linked mental retardation.
X-linked mental retardation (XLMR) is a heterogeneous disorder that affects approximately 2 in 1000 males. JARID1C/SMCX is relatively new among the known XLMR genes, and seven different mutations have been identified previously in this gene [Jensen LR et al., Am. J. Hum. Genet. 76:227-236, 2005]. Here, we report five novel JARID1C mutations in five XLMR families. The changes comprise one nonsense mutation (p.Arg332X) and four missense mutations (p.Asp87Gly; p.Phe642Leu; p.Arg750Trp; p.Tyr751Cys) affecting evolutionarily conserved amino acids. The degree of mental retardation in the affected males ranged from mild to severe, and some patients suffered from additional disorders such as epilepsy, short stature, or behavioral problems. This study brings the total number of reported JARID1C mutations to twelve. In contrast to other XLMR genes in which mutations were found only in single or very few families, JARID1C appears to be one of the more frequently mutated genes in this disorder.
Max Planck Institute for Molecular Genetics, Berlin, Germany. tzschach@molgen.mpg.de
Andreas
A
Tzschach
Steffen
S
Lenzner
Bettina
B
Moser
Richard
R
Reinhardt
Jamel
J
Chelly
Jean-Pierre
JP
Fryns
Tjitske
T
Kleefstra
Martine
M
Raynaud
Gillian
G
Turner
Hans-Hilger
HH
Ropers
Andreas
A
Kuss
Lars Riff
LR
Jensen
D000595:Amino Acid Sequence; D002648:Child; D004252:DNA Mutational Analysis; D056466:Histone Demethylases; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010089:Oxidoreductases, N-Demethylating; D010375:Pedigree; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment
D011506:Proteins; D056466:Histone Demethylases; C086877:KDM5C protein, human; D010089:Oxidoreductases, N-Demethylating