Registration of disease-associated balanced chromosome rearrangements (DBCRs) and FISH analyses of the breakpoints for positional cloning strategy.

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We registered 54 patients with "disease-associated balanced chromosome rearrangements (DBCRs)". In the study of familial 21q proximal deletion [del(21)(q11.2q21.3)], the precise deleted region was identified by FISH analyses and speculated that the USH1E mapped on 21q21 is a candidate disease locus of the proband's sensorineural hearing loss (Wakui et al. 2002). In the study of severe Prader-Willi syndrome (PWS) with monosomy 15pter-15q14 and trisomy 22pter-22q11.2, the precise deletion and duplication sizes of the derivative chromosome was determined by several FISH methods. This patient had the PWS phenotype resulted from the 15q12 deletion, and some features resulted from the partial trisomy of 22q. Intrauterine growth retardation, which is unusual in either PWS and partial trisomy of 22q, was suspected to be the effects of the deletion of 15q13-q14 (Matsumura et al. 2003). In type 2 diabetes mellitus (T2DM) patient with t(3p;9q), we constructed physical maps covering both breakpoints, and detected some candidate genes around the breakpoints. We then carried out sequence analysis for all coding regions of the candidate genes in unrelated T2DM patients in order to validate whether aberrations of the gene are common in T2DM patients, but failed to detect any pathogenic changes. In a patient having precocious puberty (PP) and mental retardation with t(7q;10p), We constructed physical maps covering both breakpoints, and detected some candidate genes. We started sequence analysis of the candidate genes in unrelated PP patients. According to the collaborations using our DBCRs samples, BPESC1, mapped on 3q23, was identified as a responsible gene for Blepharophimosis sequence (BPES) using our patient with t(3;4)(q23;p15.2) (De Baere et al. 2000). And MIPOL, mapped on 14q13, was identified as a responsible gene for mirror-image polydactyly of hands and feet using our patient with t(2;14)(p23.3;q13) (Kondoh et al. 2002).