Phenotypic expression of heterozygous lipoprotein lipase deficiency in the extended pedigree of a proband homozygous for a missense mutation.
Phenotypic expression of heterozygous lipoprotein lipase deficiency in the extended pedigree of a proband homozygous for a missense mutation.
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错义突变纯合先证者的扩展谱系中杂合脂蛋白脂肪酶缺陷的表型表达。
DOI：
10.1172/jci114770
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Lalouel,JM
中科院分区：
文献类型：
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作者：
Wilson,DE;Emi,M;Iverius,PH;Hata,A;Wu,LL;Hillas,E;Williams,RR;Lalouel,JM
家族性脂蛋白脂酶（LPL）缺乏症是一种罕见的遗传性疾病伴随着良好的特点表现。杂合型LPL缺乏症的表型表达还没有如此明确的定义。我们研究了一个先证者的家系，该先证者已知是导致无功能性LPL的突变的纯合子。126名成员的DNA与等位基因特异性探针杂交，检测到29名突变等位基因携带者。先前测量的脂肪组织LPL活性在携带者中降低了50%，但不能可靠地将其与非携带者区分开来。携带者倾向于表达一种家族性高胆固醇血症，其特征是血浆甘油三酯、VLDL胆固醇和载脂蛋白B升高，LDL和HDL胆固醇浓度降低。这些表现是年龄调制的，与运营商和非运营商之间的显着差异，观察只有在40岁以后。几个非携带者表现出类似的血脂异常，但没有极低密度脂蛋白胆固醇和低密度脂蛋白胆固醇之间的负相关关系的携带者。除了年龄和携带者状态外，潜在可逆性疾病、肥胖、高胰岛素血症和使用调脂药物也是促成因素。因此，杂合子脂蛋白脂酶缺乏，加上年龄相关的影响，可能是一种形式的家族性高脂血症。
Familial lipoprotein lipase (LPL) deficiency is a rare genetic disorder accompanied by well-characterized manifestations. The phenotypic expression of heterozygous LPL deficiency has not been so clearly defined. We studied the pedigree of a proband known to be homozygous for a mutation resulting in nonfunctional LPL. Hybridization of DNA from 126 members with allele-specific probes detected 29 carriers of the mutant allele. Adipose tissue LPL activity, measured previously, was reduced by 50% in carriers, but did not reliably distinguish them from noncarriers. Carriers were prone to the expression of a form of familial hypertriglyceridemia characterized by increased plasma triglyceride, VLDL cholesterol and apolipoprotein B, and decreased LDL and HDL cholesterol concentrations. These manifestations were age modulated, with conspicuous differences between carriers and noncarriers observed only after age 40. Several noncarriers exhibited similar lipid abnormalities, but without the inverse relationship between VLDL cholesterol and LDL cholesterol noted among carriers. In addition to age and carrier status, the potentially reversible conditions, obesity, hyperinsulinemia and lipid-raising drug use were contributory. Thus heterozygous lipoprotein lipase deficiency, together with age-related influences, may account for a form of familial hypertriglyceridemia.