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Title: Mutation analysis of the Fanconi Anemia Gene FACC

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. The authors have amplified FACC exons with their flanking 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. They have 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 [yields] 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 the study withmore » 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 [yields] T have Jewish ancestry and have a severe phenotype. 19 refs., 1 fig., 3 tabs.« less
Authors:
; ; ; ;  [1] ; ;  [2]
  1. (Rockefeller Univ., New York, NY (United States))
  2. (Guy's Hospital, London (United Kingdom))
Publication Date:
OSTI Identifier:
7105240
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Human Genetics; (United States); Journal Volume: 54:4
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ANEMIAS; GENE MUTATIONS; DNA; CROSS-LINKING; HUMAN POPULATIONS; GENETIC VARIABILITY; BIOLOGICAL VARIABILITY; CHEMICAL REACTIONS; DISEASES; HEMIC DISEASES; MUTATIONS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; POLYMERIZATION; POPULATIONS; SYMPTOMS 550400* -- Genetics