Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9

被引:53
作者
Demuth, I
Wlodarski, M
Tipping, AJ
Morgan, NV
de Winter, JP
Thiel, M
Gräsl, S
Schindler, D
D'Andrea, AD
Altay, C
Kayserili, H
Zatterale, A
Kunze, J
Ebell, W
Mathew, CG
Joenje, H
Sperling, K
Digweed, M
机构
[1] Humboldt Univ, Charite, Inst Human Genet, D-13353 Berlin, Germany
[2] Guys Kings & St Thomas Sch Med, Div Med & Mol Genet, London, England
[3] Free Univ Amsterdam, Med Ctr, Dept Clin Genet & Human Genet, Amsterdam, Netherlands
[4] Univ Wurzburg, Inst Human Genet, D-97070 Wurzburg, Germany
[5] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
[6] Hacettepe Univ, Dept Pediat, Hematol Unit, Ankara, Turkey
[7] Inst Child Hlth, Istanbul, Turkey
[8] Osped Elena dAosta, Serv Citogenet, Naples, Italy
[9] Humboldt Univ, Charite, Childrens Hosp, Berlin, Germany
关键词
Fanconi anaemia; FANCG/XRCC9; mutation screening; founder mutation;
D O I
10.1038/sj.ejhg.5200552
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-C 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-C 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.
引用
收藏
页码:861 / 868
页数:8
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