AlFadhli Suad M, Mohammed Bader, Yassin Ahmid
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University, Kuwait.
Med Princ Pract. 2008;17(5):395-9. doi: 10.1159/000141504. Epub 2008 Aug 6.
We aimed to investigate germline mutation in another extended von Hippel-Lindau (VHL) family in Kuwait with Arabian and Persian genetic admixture.
Polymerase chain reaction (PCR) followed by single-strand conformation polymorphism (SSCP) and direct sequencing of the PCR amplicons, that showed clear band shift, were used to screen the VHL gene in the index patient, 20 members of her family and 55 healthy controls of matching ethnicity.
The clinical history of all patients revealed multiple hemangioblastomas in various organs without pheochromocytomas. SSCP showed a clear band shift in 2 PCR amplicons, which were then sequenced. One was in the promoter region revealing a polymorphic site (A-123G) found as heterozygous in 40% of the healthy control subjects of the same ethnicity. The second band shift was in exon 2 seen in all clinically diagnosed VHL cases but not in the healthy members of the family or the screened healthy population. Direct sequencing revealed it was a heterozygous missense mutation G564T (Trp117Cys). Tracking the mutation in the family pedigree showed its origin from the Persian side.
This is a second missense G564T mutation in another VHL patient from Kuwait that will help expand our knowledge of the VHL gene mutation spectrum in this region of the world.
我们旨在调查科威特一个具有阿拉伯和波斯遗传混合背景的另一个von Hippel-Lindau（VHL）综合征扩展家系中的胚系突变。
采用聚合酶链反应（PCR），随后进行单链构象多态性分析（SSCP），并对显示出明显条带位移的PCR扩增产物进行直接测序，以筛查先证者、其家族的20名成员以及55名种族匹配的健康对照者中的VHL基因。
所有患者的临床病史显示各器官存在多发成血管细胞瘤，无嗜铬细胞瘤。SSCP在2个PCR扩增产物中显示出明显的条带位移，随后对其进行测序。一个位于启动子区域，发现一个多态性位点（A-123G），在相同种族的40%健康对照者中为杂合状态。第二个条带位移出现在外显子2，在所有临床诊断为VHL综合征的病例中均可见，但在家族中的健康成员或筛查的健康人群中未见。直接测序显示这是一个杂合错义突变G564T（Trp117Cys）。追踪该家系中的突变发现其源自波斯一方。
这是科威特另一名VHL综合征患者中的第二个错义突变G564T，这将有助于扩展我们对世界该地区VHL基因突变谱的认识。
