Fragile X syndrome in two siblings with major congenital malformations.
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.
Giampietro
P F
PF
Division of Medical Genetics, New York Hospital, Cornell University Medical Center, New York 10021, USA.
Haas
B R
BR
Lipper
E
E
Gutman
A
A
Zellers
N J
NJ
LaTrenta
G S
GS
Brooks
S S
SS
Matalon
R
R
Kaul
R
R
Ding
X H
XH
Brown
W T
WT
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D002675:Child, Preschool; D002971:Cleft Lip; D002972:Cleft Palate; D004933:Esophageal Atresia; D005600:Fragile X Syndrome / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D014138:Tracheoesophageal Fistula; D018911:Trinucleotide Repeats