Fragile X syndrome in two siblings with major congenital malformations

Philip F. Giampietro, Bruce R. Haas, Evelyn Lipper, Alyson Gutman, Nancy J. Zellers, Gregory S. LaTrenta, Susan Sklower Brooks, Reuben Matalon, Rajinder Kaul, Xiao Hua Ding, W. Ted Brown

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)396-400
Number of pages5
JournalAmerican Journal of Medical Genetics
Issue number2
StatePublished - May 17 1996
Externally publishedYes


  • VACTERL-H syndrome
  • fragile X syndrome
  • iduronate sulfatase
  • major congenital malformation
  • methylation mosaic

ASJC Scopus subject areas

  • Genetics(clinical)


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