Clustering of mutations responsible for branchio-oto-renal (BOR) syndrome in the eyes absent homologous region (eyaHR) of EYA1

被引:168
作者
Abdelhak, S
Kalatzis, V
Heilig, R
Compain, S
Samson, D
Vincent, C
LeviAcobas, F
Cruaud, C
LeMerrer, M
Mathieu, M
Konig, R
Vigneron, J
Weissenbach, J
Petit, C
Weil, D
机构
[1] INST PASTEUR, UNIT GENET DEFICITS SENSORIELS, CNRS URA 1968, F-75724 PARIS 15, FRANCE
[2] GENETHON HUMAN RES CTR, F-91000 EVRY, FRANCE
[3] HOP NECKER ENFANTS MALAD, UNITE RECH HANDICAPS GENET ENFANT, INSERM U393, F-75743 PARIS 15, FRANCE
[4] CTR HOSP REG UNIV AMIENS, HOP NORD, F-80054 AMIENS, FRANCE
[5] UNIV FRANKFURT KLINIKUM, INST HUMAN GENET, D-60590 FRANKFURT, GERMANY
[6] MATERNITE REG, SERV NEONATOL GENET, F-54042 NANCY, FRANCE
关键词
D O I
10.1093/hmg/6.13.2247
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
Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder, characterised by the association of branchial, otic and renal anomalies with variable degrees of severity, We have recently identified EYA1, a human homologue of the Drosophila eyes absent gene, as the gene underlying this syndrome, The products of both genes share a highly conserved 271 amino acid C-terminal region (eyaHR). The eyaHR was also found in the products of two other human genes (EYA2 and EYA3), demonstrating the existence of a novel gene family, We report here on the complete genomic structure of EYA1, This gene consists of 16 coding exons and extends over 156 kb, It encodes various alternatively spliced transcripts differing only in their 5' regions, Sequence analysis of the entire EYA1 coding region was performed for 20 unrelated patients affected by BOR syndrome, and six novel mutations were identified, Among these mutations, two are missense mutations, highlighting amino acid residues essential for the function of the EYA1 protein, and one mutation comprises a de novo Alu insertion into an exon, This insertion presumably occurs by retrotransposition, and the mobile Alu element has a poly(A) tail that is unstable throughout generations, To date, 14 mutations have been detected in BOR patients, all of which are different, However, all the mutations are located within or in the immediate vicinity of the eyaHR; the significance of this clustering is discussed.
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页码:2247 / 2255
页数:9
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