title: Fragile X syndrome in two siblings with major congenital malformations.
abstract: 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.
authors.affiliation: Division of Medical Genetics, New York Hospital, Cornell University Medical Center, New York 10021, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Giampietro
authors.forename: B R
authors.initials: BR
authors.lastname: Haas
authors.forename: E
authors.initials: E
authors.lastname: Lipper
authors.forename: A
authors.initials: A
authors.lastname: Gutman
authors.forename: N J
authors.initials: NJ
authors.lastname: Zellers
authors.forename: G S
authors.initials: GS
authors.lastname: LaTrenta
authors.forename: S S
authors.initials: SS
authors.lastname: Brooks
authors.forename: R
authors.initials: R
authors.lastname: Matalon
authors.forename: R
authors.initials: R
authors.lastname: Kaul
authors.forename: X H
authors.initials: XH
authors.lastname: Ding
authors.forename: W T
authors.initials: WT
authors.lastname: Brown
mesh_terms: 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