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Title: Fragile X syndrome in two siblings with major congenital malformations

Journal Article · · American Journal of Medical Genetics
; ;  [1]
  1. Cornell Univ. Medical Center, New York, NY (United States); and others

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. 24 refs., 4 figs.

OSTI ID:
539194
Journal Information:
American Journal of Medical Genetics, Vol. 63, Issue 2; Other Information: PBD: 17 May 1996
Country of Publication:
United States
Language:
English