Mégarbané André, Slim Rima, Nürnberg Gudrun, Ebermann Inga, Nürnberg Peter, Bolz Hanno Jörn
Université Saint-Joseph, Beirut, Lebanon.
Eur J Hum Genet. 2009 Aug;17(8):1076-9. doi: 10.1038/ejhg.2008.273. Epub 2009 Feb 4.
We have earlier described a syndrome characterized by microcephaly, cutis verticis gyrata, retinitis pigmentosa, cataracts, hearing loss and mental retardation (Mendelian inheritance in man (MIM) no: 605685) in two brothers from a non-consanguineous Lebanese family. In view of the rarity of the disorder and the high rate of inbreeding in the Lebanese population, we assumed an autosomal recessive trait inherited from a common ancestor. A genomewide scan was performed. The single locus on the long arm of chromosome 8 that showed homozygosity by descent comprised the gene responsible for Cohen syndrome (CS), VPS13B. We then sequenced VPS13B in the patients and found a homozygous splice site mutation. Several possible explanations for the overlap between CS and the clinical features observed in our patients are discussed. Our data highlight the potential of high-resolution homozygosity mapping in small populations with a high rate of inbreeding.
我们之前描述过一种综合征，其特征为小头畸形、头皮回状颅皮、色素性视网膜炎、白内障、听力丧失和智力发育迟缓（《人类孟德尔遗传》（MIM）编号：605685），该综合征出现在一个来自黎巴嫩非近亲家庭的两兄弟身上。鉴于该病症的罕见性以及黎巴嫩人群中的高近亲结婚率，我们推测这是一种从共同祖先遗传而来的常染色体隐性性状。我们进行了全基因组扫描。在8号染色体长臂上显示出同源纯合性的单个位点包含了导致科恩综合征（CS）的基因VPS13B。然后我们对患者的VPS13B进行了测序，发现了一个纯合的剪接位点突变。文中讨论了CS与我们在患者中观察到的临床特征之间重叠的几种可能解释。我们的数据突出了在近亲结婚率高的小群体中进行高分辨率纯合性定位的潜力。
