遗传与戈谢病

戈谢病

戈谢氏病是一种常染色体隐性遗传疾病,因位于1号染色体长臂上的葡糖脑苷脂酶基因的突变引起。目前为止,已明确有超过300多种变异基因[1],这些变异会引起酶的稳定性下降,或结合能力下降[2]。有相同基因型的患者,个体之间的临床表现差异很大[1]

犹太人群的发病率

尽管戈谢氏病可以发生在任何种族人群,但东欧(犹太人群)的发病率相对更高(850人中间可有一个), 而其携带者的比率可为12~15人中间有一个[1,3,4]。 4种最常见的变异类型占到犹太人群中变异类型的 89% ~ 96%[5]

戈谢氏病的遗传概率

如果父母一方为戈谢氏病基因的携带者,则每一次妊娠,有50%的概率会把变异基因传给下一代。如果父母双方均为携带者,则每一次怀孕,孩子患戈谢氏病的几率为25%[8]
下图显示戈谢氏病变异基因如何从父母传到下一代。(N:正常人;G::戈谢氏病患者;C:携带者)

遗传咨询与检测

高危人群应进行遗传咨询和DNA 检测来除外戈谢氏病。高危人群包括:戈谢氏病患者的亲属,犹太后裔以及有症状的个体[6,7]

参考文献

1.Grabowski GA. Lysosomal storage diseases. In: Braunwald E, Fauci AS, et al, eds. Harrison’s Principles of Internal Medicine. 15th ed. New York, NY: McGraw-Hill; 2001:2276-2281.

2.Beutler E, Grabowski G. Gaucher disease. In: Scriber CR, Beaudet AL, Sly WS, et al, eds. The Metabolic and Molecular Bases of Inherited Disease. 7th ed. New York, NY: McGraw-Hill; 1995;2:2641-2661.

3.National Center for Biotechnology Information. Genes and disease. Available at: http://www.ncbi.nlm.nih.gov/disease/Gaucher.html. Accessed May 2, 2002.

4.Zimran A, Gelbart T, Westwood B, et al. High frequency of the Gaucher disease mutation at nucleotide 1226 among Ashkenazi Jews. Am J Hum Genet. 1991;49:855-859.

5.Grabowski G. Gaucher disease: enzymology, genetics, and treatment. In:Harris H, Hirshchorn K, eds. Advances in Human Genetics. New York, NY: Plenum Press; 1993:377-441.

6.Morales LE. Gaucher’s disease: a review. Ann Pharmacother. 1996;30:381-388.

7.National Library of Medicine. Medical encyclopedia: Gaucher disease. Available at: www.nlm.nih.gov/medlineplus/ency/article/000564.htm. Accessed August 5, 2002.

8.Jameson JL, Kopp P. Principles of human genetics. In: Braunwald E, Fauci AS, et al, eds. Harrison’s Principles of Internal Medicine. 15th ed. New York, NY: McGraw-Hill; 2001:375-396.