Inherited interstitial duplications of proximal 15q: Genotype-phenotype correlations
Inherited interstitial duplications of proximal 15q: Genotype-phenotype correlations
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DOI：
10.1086/301624
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发表时间：
1997-12-01
影响因子：
9.8
通讯作者：
Barber, JCK
中科院分区：
文献类型：
--
作者：
Browne, CE;Dennis, NR;Barber, JCK
我们介绍了20例15号染色体长臂近端间质重复的无关患者的细胞遗传学、分子细胞遗传学和分子遗传学结果。多种探针显示，在20例患者中有4例重复区域包含普拉德 - 威利/安格尔曼关键区域（PWACR），这些患者均确诊有发育迟缓。在其中一名患者的两名患病同胞中发现了重复，但在三名未患病的同胞中未发现。所有四名先证者的重复均遗传自其母亲，其中三名母亲也患病。两名患病母亲也携带母系遗传的重复，而未患病母亲和一名未患病祖母的重复源自父亲，这增加了亲本来源效应的可能性。在其余16例患者中未发现PWACR重复，其中4例因发育迟缓被转诊。在可获得亲本样本的14个家庭中，重复从表型正常的亲本（母亲或父亲）遗传的频率相同。对两名患者进行的比较基因组杂交表明，PWACR之外的15q近端是重复物质的来源。使用PWACR探针可区分一大组无明显临床意义的重复和一小组重复，在后者中，母系来源的PWACR重复始终与发育迟缓和语言困难相关，但与普拉德 - 威利综合征或安格尔曼综合征的明显特征无关。
We present the cytogenetic, molecular cytogenetic, and molecular genetic results on 20 unrelated patients with an interstitial duplication of the proximal long arm of chromosome 15. Multiple probes showed that the Prader-Willi/Angelman critical region (PWACR) was included in the duplication in 4/20 patients, each ascertained with developmental delay. The duplication was also found in two affected but not in three unaffected sibs of one of these patients. All four probands had inherited their duplication from their mothers, three of whom were also affected. Two of the affected mothers also carried a maternally inherited duplication, whereas the duplication in the unaffected mother and in an unaffected grandmother was paternal in origin, raising the possibility of a parental-origin effect. The PWACR was not duplicated in the remaining 16 patients, of whom 4 were referred with developmental delay. In the 14 families for which parental samples were available, the duplication was inherited with equal frequency from a phenotypically normal parent, mother or father. Comparative genomic hybridization undertaken on two patients suggested that proximal 15q outside the PWACR was the origin of the duplicated material. The use of PWACR probes discriminates between a large group of duplications of no apparent clinical significance and a smaller group, in which a maternally derived PWACR duplication is consistently associated with developmental delay and speech difficulties but not with overt features of either Prader-Willi syndrome or Angelman syndrome.