Lagier-Tourenne C, Boltshauser E, Breivik N, Gribaa M, Bétard C, Barbot C, Koenig M
IGBMC, CNRS/INSERM/ULP, Illkirch, C.U. de Strasbourg, France.
J Med Genet. 2004 Apr;41(4):273-7. doi: 10.1136/jmg.2003.014787.
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.
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.
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.
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.
Joubert综合征（JS）是一种隐性遗传疾病，其特征为出生时肌张力减退和发育迟缓，随后出现躯干共济失调和认知障碍、典型的神经影像学表现（小脑蚓部发育不全，“磨牙征”）以及特征性面部特征。JS在临床上具有异质性，一些患者在新生儿期出现呼吸异常、眼球运动失用、视网膜营养不良、视网膜缺损、上睑下垂、多指畸形以及肾单位肾痨或囊性发育不良性肾病。JS在遗传上也具有异质性，已知的两个基因座分别位于9q34（JBTS1）和11p11 - q12（CORS2），但仅涵盖部分病例。
对一个大型近亲Joubert家族（5名患者）进行全基因组标记连锁分析，并随后对16个较小家族进行候选基因座检测。
我们通过对两个近亲家族的研究，在此报告在6q23区域发现了第三个基因座（JBTS3）。计算包括近亲环在内的LOD得分，两个家族在q = 0时分别得到最大值4.1和2.3。
证实了疾病与跨越13.1 cM区间的D6S1620 - D6S1699单倍型之间存在连锁关系。基因型 - 表型研究表明，与CORS2不同，JBTS3似乎与肾功能障碍无关。
