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 journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)396-400
Number of pages5
JournalAmerican Journal of Medical Genetics
Volume63
Issue number2
DOIs
StatePublished - May 17 1996
Externally publishedYes

Fingerprint

Fragile X Syndrome
Iduronate Sulfatase
Chromosomes
Trinucleotide Repeats
Esophageal Atresia
Mosaicism
Cleft Lip
Ventricular Heart Septal Defects
Constitution and Bylaws
Cleft Palate
Southern Blotting
Methylation
Fistula
Down-Regulation
Polymerase Chain Reaction
Mutation
Enzymes
Genes
VACTERL association
Thumb deformity

Keywords

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

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)
  • Neuropsychology and Physiological Psychology

Cite this

Giampietro, P. F., Haas, B. R., Lipper, E., Gutman, A., Zellers, N. J., LaTrenta, G. S., ... Brown, W. T. (1996). Fragile X syndrome in two siblings with major congenital malformations. American Journal of Medical Genetics, 63(2), 396-400. https://doi.org/10.1002/(SICI)1096-8628(19960517)63:2<396::AID-AJMG14>3.0.CO;2-F

Fragile X syndrome in two siblings with major congenital malformations. / Giampietro, Philip F.; Haas, Bruce R.; Lipper, Evelyn; Gutman, Alyson; Zellers, Nancy J.; LaTrenta, Gregory S.; Sklower Brooks, Susan; Matalon, Reuben; Kaul, Rajinder; Ding, Xiao Hua; Brown, W. Ted.

In: American Journal of Medical Genetics, Vol. 63, No. 2, 17.05.1996, p. 396-400.

Research output: Contribution to journalArticle

Giampietro, PF, Haas, BR, Lipper, E, Gutman, A, Zellers, NJ, LaTrenta, GS, Sklower Brooks, S, Matalon, R, Kaul, R, Ding, XH & Brown, WT 1996, 'Fragile X syndrome in two siblings with major congenital malformations', American Journal of Medical Genetics, vol. 63, no. 2, pp. 396-400. https://doi.org/10.1002/(SICI)1096-8628(19960517)63:2<396::AID-AJMG14>3.0.CO;2-F
Giampietro, Philip F. ; Haas, Bruce R. ; Lipper, Evelyn ; Gutman, Alyson ; Zellers, Nancy J. ; LaTrenta, Gregory S. ; Sklower Brooks, Susan ; Matalon, Reuben ; Kaul, Rajinder ; Ding, Xiao Hua ; Brown, W. Ted. / Fragile X syndrome in two siblings with major congenital malformations. In: American Journal of Medical Genetics. 1996 ; Vol. 63, No. 2. pp. 396-400.
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