Positional cloning of a novel gene on chromosome 16q causing Bardet-Biedl syndrome (BBS2)
Positional cloning of a novel gene on chromosome 16q causing Bardet-Biedl syndrome (BBS2)
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DOI：
10.1093/hmg/10.8.865
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发表时间：
2001-04-01
影响因子：
3.5
通讯作者：
Sheffield, VC
中科院分区：
文献类型：
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作者：
Nishimura, DY;Searby, CC;Sheffield, VC
Bardet-Biedl综合征(BBS)是一种遗传异质性的常染色体隐性遗传病，其主要临床特征为肥胖、视网膜色素沉着、多指、发育不全、智力低下和肾脏异常。这种疾病的相关特征包括糖尿病、高血压和先天性心脏病。已知有6个BBS基因座，定位在第2、3、11、15、15和20号染色体上。BBS2基因座最初被定位在16q21染色体上18 cM的区间，与一个大的近交贝都因人系。对贝都因群体的进一步分析允许将该基因座精细定位到标记D16S408远端2 cM的区域。对该区域的物理作图和序列分析导致了一些已知基因和表达序列标签簇的鉴定。对一个具有广泛组织表达模式的新基因(BBS2)的突变筛选发现，在两个近交系中存在纯合子突变，其中包括用于初步鉴定BBS2基因座的大贝都因家系。此外，在来自小核心家庭的18个无关的BBS先证者中，有3个发现了突变。
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive disorder with the primary clinical features of obesity, pigmented retinopathy, polydactyly, hypogenitalism, mental retardation and renal anomalies. Associated features of the disorder include diabetes mellitus, hypertension and congenital heart disease. There are six known BBS loci, mapping to chromosomes 2, 3, 11, 15, 15 and 20. The BBS2 locus was initially mapped to an 18 cM interval on chromosome 16q21 with a large inbred Bedouin kindred. Further analysis of the Bedouin population allowed for the fine mapping of this locus to a 2 cM region distal to marker D16S408. Physical mapping and sequence analysis of this region resulted in the identification of a number of known genes and expressed sequence tag clusters. Mutation screening of a novel gene (BBS2) with a wide pattern of tissue expression revealed homozygous mutations in two inbred pedigrees, including the large Bedouin kindred used to initially identify the BBS2 locus. In addition, mutations were found in three of 18 unrelated BBS probands from small nuclear families.