Homozygosity mapping of a third Joubert syndrome locus to 6q23
Homozygosity mapping of a third Joubert syndrome locus to 6q23
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DOI：
10.1136/jmg.2003.014787
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发表时间：
2004-04-01
影响因子：
4
通讯作者：
Koenig, M
中科院分区：
文献类型：
--
作者：
Lagier-Tourenne, C;Boltshauser, E;Koenig, M
背景：Joubert 综合征 (JS) 是一种隐性遗传性疾病，其特征是出生时肌张力低下和发育迟缓，随后出现躯干共济失调和认知障碍、特征性神经影像学表现（小脑蚓部发育不全、“磨牙征”）和提示性面部特征。JS 具有临床异质性，部分患者表现为新生儿期呼吸异常、动眼神经失用、视网膜营养不良、视网膜缺损、上睑下垂、六趾畸形、肾痨或囊性发育不良性肾脏也具有遗传异质性，在 9q34 (JBTS1) 和 11p11-q12 (CORS2) 上有两个已知基因座，仅代表一小部分病例。方法：对一个大的近亲 Joubert 家族（五个受影响）进行了与覆盖整个基因组的标记集的连锁分析，随后对 16 个较小的家族进行了候选基因检测。结果：我们在此报告了从两个近亲家族 LOD 评分计算的研究中鉴定出的 6q23 (JBTS3) 中的第三个基因座，包括血缘环，在 q=0 时两个家族的最大值分别为 4.1 和 2.3。结论：该疾病与跨越 13.1 的 D6S1620-D6S1699 单倍型之间的关联。基因型-表型研究表明，与 CORS2 不同，JBTS3 似乎与肾功能障碍无关。
Background: Joubert syndrome (JS) is a recessively inherited disorder characterised by hypotonia at birth and developmental delay, followed by truncal ataxia and cognitive impairment, characteristic neuroimaging findings (cerebellar vermis hypoplasia, "molar tooth sign'') and suggestive facial features. JS is clinically heterogeneous with some patients presenting with breathing abnormalities in the neonatal period, oculomotor apraxia, retinal dystrophy, retinal coloboma, ptosis, hexadactyly, and nephronophtisis or cystic dysplastic kidneys. JS is also genetically heterogeneous, with two known loci, on 9q34 (JBTS1) and 11p11-q12 (CORS2), representing only a fraction of cases.Methods: A large consanguineous Joubert family (five affected) was analysed for linkage with a marker set covering the entire genome and 16 smaller families were subsequently tested for candidate loci.Results: We report here the identification of a third locus in 6q23 (JBTS3) from the study of two consanguineous families. LOD score calculation, including the consanguinity loops, gave a maximum value of 4.1 and 2.3 at q=0 for the two families, respectively.Conclusions: Linkage between the disease and the D6S1620-D6S1699 haplotype spanning a 13.1 cM interval is demonstrated. Genotype-phenotype studies indicate that, unlike CORS2, JBTS3 appears not to be associated with renal dysfunction.