Disruption of chromodomain helicase DNA binding protein 2 (CHD2) causes scoliosis.
Herein we characterize an apparently balanced de novo translocation, t(X;15)(p22.2;q26.1)dn, in a female patient with scoliosis, hirsutism, learning problems, and developmental delay (DGAP025). Other clinical findings include a high-arched palate, 2-3 syndactyly of the toes, and mildly elevated serum testosterone. No known or predicted genes are disrupted by the Xp22.2 breakpoint. The 15q26.1 breakpoint disrupts chromodomain helicase DNA binding protein 2 (CHD2). Another member of the chromatin-remodeling gene family, CHD7, has been associated with a defined constellation of congenital anomalies known as coloboma, heart anomaly, choanal atresia, mental retardation, genital and ear anomalies syndrome (CHARGE) and idiopathic scoliosis. Monosomy of 15q26 also has been associated with a spectrum of congenital abnormalities and growth retardation that overlaps with those of DGAP025. To provide a biological correlate, we characterized a mutant mouse model with Chd2 disruption that is associated with embryonic and perinatal lethality. Expression analysis indicated that Chd2 is expressed in the heart, forebrain, extremities, facial and dorsal regions during specific times of embryonic development. Chd2(+/m) mice showed pronounced lordokyphosis, reduced body fat, postnatal runting, and growth retardation. These data suggest that haploinsufficiency for CHD2 could result in a complex of abnormal human phenotypes that includes scoliosis and possibly features similar to CHARGE syndrome.
Kulkarni
Shashikant
S
Division of Women's and Perinatal Pathology and Clinical Cytogenetics Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Nagarajan
Prabakaran
P
Wall
Jonathan
J
Donovan
Diana J
DJ
Donell
Robert L
RL
Ligon
Azra H
AH
Venkatachalam
Sundaresan
S
Quade
Bradley J
BJ
D000293:Adolescent; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D004265:DNA Helicases / Q000172:deficiency* / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006628:Hirsutism / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007859:Learning Disabilities / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010641:Phenotype; D012600:Scoliosis / Q000235:genetics* / Q000378:metabolism*; D014178:Translocation, Genetic
C514205:Chd2 protein, mouse; D017931:DNA Primers; D004268:DNA-Binding Proteins; D004265:DNA Helicases