RESUMO
PURPOSE: The purpose of the study was to look for ADAMTSL4 mutations in a cohort of German patients with isolated ectopia lentis from nonconsanguineous families. METHODS: Mutation screening was performed by PCR amplification of the coding exons of ADAMTSL4 and subsequent sequencing. RESULTS: An identical homozygous deletion of 20 bp of coding sequence within exon 6 (NM_019032.4:c.759_778del20) was identified in eight individuals from seven unrelated families. In a screen of 360 ethnically matched, unaffected individuals, two heterozygous mutation carriers were found. The mutation was always accompanied by the identical haplotype, suggestive of a founder mutation. CONCLUSIONS: The results emphasize the association of ADAMTSL4 null mutations with isolated ectopia lentis and the presence of a founder mutation in the European population. Screening of ADAMTSL4 should be considered in all patients with isolated ectopia lentis, with or without family history. In patients from nonconsanguineous families, the authors propose a two-step diagnostic approach, starting with an examination of exon 6 before sequencing the entire coding region of ADAMTSL4.
Assuntos
Ectopia do Cristalino/genética , Efeito Fundador , Deleção de Genes , Trombospondinas/genética , Proteínas ADAMTS , Criança , Pré-Escolar , Análise Mutacional de DNA , Éxons/genética , Feminino , Genótipo , Homozigoto , Humanos , Lactente , Recém-Nascido , Masculino , Repetições de Microssatélites , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Array-based comparative genome hybridization is a powerful tool for detecting chromosomal imbalances at high resolution. However, the design and setup of such arrays are time consuming and expensive and thus worthwhile only when large numbers of arrays will be processed. To provide a feasible solution, we have developed an algorithm that renders the publicly available Affymetrix 10K SNP genotyping chip useful for high-resolution analysis of chromosomal imbalances. We have used our newly developed algorithm to analyze data from Affymetrix 10K chips that were hybridized with DNA probes from a variety of different sources, such as primary tumors, cell lines, and blood from patients with unbalanced translocations. In summary, we were able to (i) demonstrate the capability of our method by reproduction of published and unpublished data obtained with alternative methods and (ii) identify novel imbalances that were not shown before.
