Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel.
J Inherit Metab Dis. 2010 Feb;33(1):79-83. doi: 10.1007/s10545-009-9024-7. Epub 2010 Jan 5.
The only prognostic markers in Gaucher disease, the most common lysosomal storage disorder, are young age at first symptom/sign and the presence of null/severe mutations, both being predictive of more severe phenotypes. Therefore, it would be helpful to know whether siblings with the same genotype can be expected to experience comparable phenotypic expression. All non-neuronopathic sibling pairs in our referral clinic (1993-2008) with the same genotype were included. For each pair, gender, date of birth, severity score index at presentation, age at diagnosis and first symptom/sign, presence of bone involvement, spleen status, and use of enzyme replacement therapy were tabulated. There were 90 pairs of siblings: two sets of identical twins; 24 pairs of brothers, 24 pairs of sisters, and 42 pairs of mixed gender. For all measures of disease severity used, only in sibling pairs with an older sister and a younger brother were phenotypes significantly different between siblings. Thus, this large cohort of sibling pairs with type 1 Gaucher disease confirmed that, in general, the phenotypic expression in the younger sibling will be similar enough to that of an older affected sibling that genetic counseling may use those findings in a prognostic way.
戈谢氏病是最常见的溶酶体贮积症，目前唯一的预后标志物是首发症状/体征的年龄较小和存在无效/严重突变，两者均提示更严重的表型。因此，了解具有相同基因型的同胞是否可能出现可比的表型表达是有帮助的。纳入了我院（1993-2008 年）就诊的所有具有相同基因型的非神经病变同胞对。对于每一对，记录了性别、出生日期、就诊时的严重程度评分指数、诊断年龄和首发症状/体征、是否存在骨骼受累、脾脏状态以及是否使用酶替代疗法。共有 90 对同胞：两对同卵双胞胎；24 对兄弟，24 对姐妹，42 对混合性别。对于使用的所有疾病严重程度指标，只有姐姐和弟弟年龄相差较大的同胞对之间，表型存在显著差异。因此，本研究中这一大群 1 型戈谢氏病的同胞对证实，一般来说，年幼同胞的表型表达与受影响的年长同胞足够相似，遗传咨询可以根据这些发现进行预后评估。
