A MUTATION IN THE HUMAN GLUCOCEREBROSIDASE GENE IN NEURONOPATHIC GAUCHERS-DISEASE
A MUTATION IN THE HUMAN GLUCOCEREBROSIDASE GENE IN NEURONOPATHIC GAUCHERS-DISEASE
复制标题
DOI：
10.1056/nejm198703053161002
复制
发表时间：
1987-03-05
影响因子：
158.5
通讯作者：
GINNS, EI
中科院分区：
文献类型：
--
作者：
TSUJI, S;CHOUDARY, PV;GINNS, EI
为了寻找2型戈谢病（急性神经病型）的遗传标记，我们将来自戈谢病患者的葡萄糖脑苷脂酶基因克隆的核苷酸序列与正常基因进行了比较。我们发现只有一个单一的碱基替换（T →）。C）外显子X。该突变导致第444位上的亮氨酸被脯氨酸取代，并产生了一个新的用于NH3限制性内切酶的切割位点。我们分析了20例1型、5例2型和11例3型高雪氏病患者基因瘤DNA的限制性片段长度多态性（RFLP）。5例2型疾病患者中有4例和所有11例3型疾病患者至少有一个等位基因突变。2/5例2型糖尿病患者和7/11例3型糖尿病患者为该突变纯合子。20例1型高雪氏病患者中只有4例携带该突变等位基因且为杂合子，29例正常对照者中无一例携带该突变等位基因。这种突变的高频率（444亮氨酸→亮氨酸）是由于突变的高频率（444亮氨酸→亮氨酸）引起的。脯氨酸）的检测，可能对鉴别高歇氏病的神经系统后遗症患者有价值。
To search for a genetic marker for type 2 Gaucher''s disease (acute neuropathic form), we compared the nucleotide sequence of a cloned glucocerebrosidase gene from a patient with Gaucher''s disease with a normal gene. We found only a single base substitution (T .fwdarw. C) in exon X. This mutation results in the substitution of proline for leucine in position number 444 and produces a new cleavage site for the Ncil restriction endonuclease. We analyzed Ncil enzymatic digests of genoma DNA from 20 patients with type 1, 5 with type 2, and 11 with type 3 Gaucher''s disease, and 29 normal controls for a restriction-fragment-length polymorphism (RFLP). Four of 5 patients with type 2 disease and all 11 with type 3 disease had at least one allele with the mutation. Two of 5 patients with type 2 disease and 7 of 11 with type 3 were homozygous for this mutation. Only 4 of 20 patients with type 1 Gaucher''s disease had the mutant allele and were heterozygous for it. None of the 29 normal controls had the mutant allele. The high frequency of this mutation (444leucine .fwdarw. proline) in patients with neuropathic Gaucher''s disease, detectable by the Ncil RFLP, may be of value in the identification of patients who will have the neurologic sequelae of Gaucher''s disease.