TY - JOUR
T1 - Fragile X syndrome in two siblings with major congenital malformations
AU - Giampietro, Philip F.
AU - Haas, Bruce R.
AU - Lipper, Evelyn
AU - Gutman, Alyson
AU - Zellers, Nancy J.
AU - LaTrenta, Gregory S.
AU - Sklower Brooks, Susan
AU - Matalon, Reuben
AU - Kaul, Rajinder
AU - Ding, Xiao Hua
AU - Brown, W. Ted
PY - 1996/5/17
Y1 - 1996/5/17
N2 - We report on 2 brothers with both fragile X and VACTERL-H syndrome. The first sibling, age 5, had bilateral cleft lip and palate, ventricular septal defect, and a hypoplastic thumb. The second sibling, age 2 1/2 , had a trachesophageal fistula, esophageal atresia, and vertebral abnormality. High- resolution chromosome analysis showed a 46, XY chromosome constitution in both siblings. By PCR and Southern blot analysis, the siblings were found to have large triplet repeat expansions in the fragile X gene (FMR 1) and both had methylation mosaicism. Enzyme kinetic studies of iduronate sulfatase demonstrated a two-fold increase in activity in the first sib as compared to the second. Possible mechanisms through which the fragile X mutation can cause down-regulation of adjacent loci are discussed.
AB - We report on 2 brothers with both fragile X and VACTERL-H syndrome. The first sibling, age 5, had bilateral cleft lip and palate, ventricular septal defect, and a hypoplastic thumb. The second sibling, age 2 1/2 , had a trachesophageal fistula, esophageal atresia, and vertebral abnormality. High- resolution chromosome analysis showed a 46, XY chromosome constitution in both siblings. By PCR and Southern blot analysis, the siblings were found to have large triplet repeat expansions in the fragile X gene (FMR 1) and both had methylation mosaicism. Enzyme kinetic studies of iduronate sulfatase demonstrated a two-fold increase in activity in the first sib as compared to the second. Possible mechanisms through which the fragile X mutation can cause down-regulation of adjacent loci are discussed.
KW - VACTERL-H syndrome
KW - fragile X syndrome
KW - iduronate sulfatase
KW - major congenital malformation
KW - methylation mosaic
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U2 - 10.1002/(SICI)1096-8628(19960517)63:2<396::AID-AJMG14>3.0.CO;2-F
DO - 10.1002/(SICI)1096-8628(19960517)63:2<396::AID-AJMG14>3.0.CO;2-F
M3 - Article
C2 - 8725793
AN - SCOPUS:0029980186
SN - 0148-7299
VL - 63
SP - 396
EP - 400
JO - American Journal of Medical Genetics
JF - American Journal of Medical Genetics
IS - 2
ER -