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| MUTATION ANALYSIS OF THE FANCONI-ANEMIA GENE FACC |
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| Author(s): VERLANDER PC, LIN JD, UDONO MU, ZHANG Q, GIBSON RA, MATHEW CG, AUERBACH AD |
| Source: AMERICAN JOURNAL OF HUMAN GENETICS Volume: 54 Issue: 4 Pages: 595-601 Published: APR 1994 |
| Times Cited: 101 References: 19 |
| Abstract: Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive disorder characterized by a unique hypersensitivity of cells to DNA cross-linking agents; a gene for complementation group C (FACC) has recently been cloned. We have amplified FACC exons with their nanking intron sequences from genomic DNA from 174 racially and ethnically diverse families in the International Fanconi Anemia Registry and have screened for mutations by using SSCP analysis. We identified eight different variants in 32 families; three were detected in exon 1, one in exon 4, one in intron 4, two in exon 6, and one in exon 14. Two of the eight variants, in seven families, did not segregate with the disease allele in multiplex families, suggesting that these variants represented benign polymorphisms. Disease-associated mutations in FACC were detected in a total of 25 (14.4%) of 174 families screened. The most frequent mutations were IVS4 +4 A-->T (intron 4; 12 families) and 322delG (exon 1; 9 families). Other, less common mutations include Q13X in exon 1, R185X and D195V in exon 6, and L554P in exon 14. The polymorphisms were S26F in exon 1 and G139E in exon 4. All patients in our study with 322delG, Q13X, R185X, and D195V are of northern or eastern European or southern Italian ancestry, and 18 of 19 have a mild form of the disease, while the 2 patients with L554P, both from the same family, have a severe phenotype. All 19 patients with IVS4 +4 A-->T have Jewish ancestry and have a severe phenotype. |
| Document Type: Article |
| Language: English |
| Reprint Address: VERLANDER, PC (reprint author), ROCKEFELLER UNIV, INVEST DERMATOL LAB, 1230 YORK AVE, BOX H30, NEW YORK, NY 10021 USA |
Addresses:
1. UNITED MED & DENT SCH GUYS & ST THOMAS HOSP, GUYS HOSP, DIV MED & MOLEC GENET, LONDON, ENGLAND |
| Publisher: UNIV CHICAGO PRESS, 5720 S WOODLAWN AVE, CHICAGO, IL 60637 |
| Subject Category: Genetics & Heredity |
| IDS Number: NC836 |
| ISSN: 0002-9297 |
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