Novel mutation and three other sequence variants segregating with phenotype at keratoconus 13q32 susceptibility locus

被引:60
作者
Czugala, Marta [1 ]
Karolak, Justyna A. [1 ]
Nowak, Dorota M. [1 ]
Polakowski, Piotr [2 ]
Pitarque, Jose [3 ]
Molinari, Andrea [3 ]
Rydzanicz, Malgorzata [1 ]
Bejjani, Bassem A. [4 ]
Yue, Beatrice Y. J. T. [5 ]
Szaflik, Jacek P. [2 ]
Gajecka, Marzena [1 ]
机构
[1] Polish Acad Sci, Inst Human Genet, PL-60479 Poznan, Poland
[2] Med Univ Warsaw, Dept Ophthalmol, Warsaw, Poland
[3] Hosp Metropolitano, Dept Ophthalmol, Quito, Ecuador
[4] Signature Genom, Spokane, WA USA
[5] Univ Illinois, Coll Med, Dept Ophthalmol & Visual Sci, Chicago, IL USA
关键词
keratoconus; keratoconus gene; 13q32; locus; DOCK9; IPO5; STK24; AUTOSOMAL-DOMINANT KERATOCONUS; MAMMALIAN STE20-LIKE PROTEIN-KINASE-3; NUCLEOTIDE EXCHANGE FACTORS; LEBER CONGENITAL AMAUROSIS; FAMILIAL KERATOCONUS; PROTEIN-KINASE; LINKAGE SCAN; GENE; IDENTIFICATION; EXPRESSION;
D O I
10.1038/ejhg.2011.203
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
Keratoconus (KTCN), a non-inflammatory corneal disorder characterized by stromal thinning, represents a major cause of corneal transplantations. Genetic and environmental factors have a role in the etiology of this complex disease. Previously reported linkage analysis revealed that chromosomal region 13q32 is likely to contain causative gene(s) for familial KTCN. Consequently, we have chosen eight positional candidate genes in this region: MBNL1, IPO5, FARP1, RNF113B, STK24, DOCK9, ZIC5 and ZIC2, and sequenced all of them in 51 individuals from Ecuadorian KTCN families and 105 matching controls. The mutation screening identified one mutation and three sequence variants showing 100% segregation under a dominant model with KTCN phenotype in one large Ecuadorian family. These substitutions were found in three different genes: c. 2262>4C (p. Gln754His) and c.720+43A>G in DOCK9; c.2377-132A>C in IPO5 and c.1053+29G>C in STK24. PolyPhen analyses predicted that c. 2262A>C (Gln754His) is possibly damaging for the protein function and structure. Our results suggest that c. 2262A>C (p. Gln754His) mutation in DOCK9 may contribute to the KTCN phenotype in the large KTCN-014 family. European Journal of Human Genetics (2012) 20, 389-397; doi: 10.1038/ejhg.2011.203; published online 2 November 2011
引用
收藏
页码:389 / 397
页数:9
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