Fragile X syndrome in two siblings with major congenital malformations
- 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, Journal Name: American Journal of Medical Genetics Journal Issue: 2 Vol. 63; ISSN 0148-7299; ISSN AJMGDA
- Country of Publication:
- United States
- Language:
- English
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