Reshef A, Meiner V, Berginer V M, Leitersdorf E
Division of Medicine, Hadassah University Hospital, Jerusalem, Israel.
J Lipid Res. 1994 Mar;35(3):478-83.
Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive sterol storage disease characterized by the accumulation of a bile alcohol, cholestanol, in diverse tissues. The disorder is manifested by extensive nervous system involvement, juvenile cataracts, tendon xanthomas, and premature atherosclerosis and is caused by sterol 27-hydroxylase (EC 1.14.13.15) mutations. Recently, two mutations were shown to cause CTX in four Jewish families of Moroccan origin. An additional mutant allele, found in a Jewish family of Algerian origin is characterized here. Sequence analysis revealed a C to T transition at cDNA position 1037 which predicted a threonine to methionine substitution at residue 306 (designated T306M). It is highly suggestive, but not definitive, that this transition is the mutation causing CTX in this family. A search for additional cases from Jewish families of North African extraction identified five new families including 10 cases. The three sterol 27-hydroxylase gene mutations account for all 10 CTX families and their presence may suggest the existence of positive selective forces that lead to an increased prevalence of this relatively rare disease in Jews from North Africa.
脑腱黄瘤病（CTX）是一种常染色体隐性遗传的固醇贮积病，其特征是胆汁醇胆甾烷醇在多种组织中蓄积。该疾病表现为广泛的神经系统受累、青少年白内障、腱黄瘤和早发性动脉粥样硬化，由固醇27 - 羟化酶（EC 1.14.13.15）突变引起。最近，在四个摩洛哥裔犹太家庭中发现了两种导致CTX的突变。本文对在一个阿尔及利亚裔犹太家庭中发现的另一个突变等位基因进行了特征描述。序列分析显示，cDNA位置1037处发生了C到T的转变，预测第306位残基由苏氨酸替换为甲硫氨酸（命名为T306M）。高度提示但不确定的是，这种转变是导致该家庭患CTX的突变。对来自北非裔犹太家庭的其他病例进行筛查，发现了五个新家庭，包括10个病例。这三种固醇27 - 羟化酶基因突变解释了所有10个CTX家庭的情况，它们的存在可能表明存在正向选择力，导致这种相对罕见的疾病在北非犹太人中的患病率增加。
