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

我们登记了54例“疾病相关的平衡染色体重排(DBCRs)”患者。在家族性21q近端缺失[del(21)(q11.2q21.3)]的研究中，通过FISH分析确定了精确的缺失区域，推测21q21上的USH1E是先证者感音神经性耳聋的候选疾病基因(Wakui等人)。2002年)。在重度Prader-Willi综合征(PWS)的研究中，用多种FISH方法测定了衍生染色体的精确缺失和重复大小。此例患者的PWS表型源于15q12缺失，部分特征源于22q的部分三体。宫内发育迟缓，在PWS和22q部分三体中都是罕见的，被怀疑是15q13-q14缺失的影响(MatSumura等人)。2003年)。在具有t(3p；9q)的2型糖尿病(T2 DM)患者中，我们构建了覆盖两个断裂点的物理图谱，并在断裂点附近检测到一些候选基因。然后，我们对无关T2 DM患者候选基因的所有编码区进行了序列分析，以验证该基因的异常是否在T2 DM患者中常见，但未能检测到任何致病变化。在一个患有性早熟和智力低下的t(7q；10p)患者中，我们构建了覆盖这两个断裂点的物理图谱，并检测到了一些候选基因。我们开始对无关PP患者的候选基因进行序列分析。根据使用我们的DBCRs样本的合作，定位于3q23的BPESC1被鉴定为与t(3；4)(q23；p15.2)(de Baere等人)的BPES序列(BPES)有关的基因。2000)。在我们的t(2；14)(p23.3；q13)患者中，定位于14q13的Mipol1基因被鉴定为手足镜像多指畸形的致病基因(Kondoh et al.2002年)。

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).