title: Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9.
abstract: FANCG was the third Faconi anaemia gene identified and proved to be identical to the previously cloned XRCC9 gene. We present the pathogenic mutations and sequence variants we have so far identified in a panel of FA-G patients. Mutation screening was performed by PCR, single strand conformational polymorphism analysis and protein truncation tests. Altogether 18 mutations have been determined in 20 families - 97% of all expected mutant alleles. All mutation types have been found, with the exception of large deletions, the large majority is predicted to lead to shortened proteins. One stop codon mutation, E105X, has been found in several German patients and this founder mutation accounts for 44% of the mutant FANCG alleles in German FA-G patients. Comparison of clinical phenotypes shows that patients homozygous for this mutation have an earlier onset of the haematological disorder than most other FA-G patients. The mouse Fancg sequence was established in order to evaluate missense mutations. A putative missense mutation, L71P, in a possible leucine zipper motif may affect FANCG binding of FANCA and seems to be associated with a milder clinical phenotype.
authors.affiliation: Institute of Human Genetics, Charité, Campus Virchow, Humboldt University, Berlin, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Demuth
authors.forename: M
authors.initials: M
authors.lastname: Wlodarski
authors.forename: A J
authors.initials: AJ
authors.lastname: Tipping
authors.forename: N V
authors.initials: NV
authors.lastname: Morgan
authors.forename: J P
authors.initials: JP
authors.lastname: de Winter
authors.forename: M
authors.initials: M
authors.lastname: Thiel
authors.forename: S
authors.initials: S
authors.lastname: Gräsl
authors.forename: D
authors.initials: D
authors.lastname: Schindler
authors.forename: A D
authors.initials: AD
authors.lastname: D'Andrea
authors.forename: C
authors.initials: C
authors.lastname: Altay
authors.forename: H
authors.initials: H
authors.lastname: Kayserili
authors.forename: A
authors.initials: A
authors.lastname: Zatterale
authors.forename: J
authors.initials: J
authors.lastname: Kunze
authors.forename: W
authors.initials: W
authors.lastname: Ebell
authors.forename: C G
authors.initials: CG
authors.lastname: Mathew
authors.forename: H
authors.initials: H
authors.lastname: Joenje
authors.forename: K
authors.initials: K
authors.lastname: Sperling
authors.forename: M
authors.initials: M
authors.lastname: Digweed
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005199:Fanconi Anemia / Q000235:genetics*; D052241:Fanconi Anemia Complementation Group G Protein; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017386:Sequence Homology, Amino Acid
chemical_list: D004268:DNA-Binding Proteins; C499909:FANCG protein, human; D052241:Fanconi Anemia Complementation Group G Protein; D004247:DNA