Hereditary inclusion body myopathy - The Middle Eastern genetic cluster
Hereditary inclusion body myopathy - The Middle Eastern genetic cluster
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DOI：
10.1212/01.wnl.0000061617.71839.42
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发表时间：
2003-05-13
期刊：
影响因子：
9.9
通讯作者：
Mitrani-Rosenbaum, S
中科院分区：
文献类型：
--
作者：
Argov, Z;Eisenberg, L;Mitrani-Rosenbaum, S
背景：股四头肌保留的隐性遗传性包涵体肌病 (HIBM) 最初仅在来自波斯地区的犹太人中被描述。最近鉴定出导致这种肌病的基因和常见的“波斯犹太人突变”（M712T），使得能够重新评估中东各个社区的非典型表型和 HIBM 的流行病学。目的：检测中东 HIBM 患者 DNA 中的 M712T 突变。方法：对所有疑似 HIBM 患者的 DNA 进行 M712T 突变检测。经基因证明具有 HIBM 的未受影响的家庭成员也接受了研究。在大多数家族中，使用跨越 HIBM 基因 700 kb 区域的标记进行单倍型构建。结果：来自 55 个家族（中东犹太人、卡拉派以及巴勒斯坦和贝都因血统的阿拉伯穆斯林）的 129 名 HIBM 患者为 M712T 突变纯合子，并且都携带相同的单倍型。五名临床上未受影响的受试者对于常见突变和单倍型也是纯合的，其中包括两名老年人（年龄 50 岁和 68 岁）。具有相同突变的非典型特征是五名患者明显的股四头肌无力，两名患者仅近端无力，三名患者面部无力，一名患者的肌肉活检显示血管周围炎症。结论：隐性 HIBM 的表型谱比之前描述的更宽，这种肌病的诊断标准必须改变。中东集群是创始人突变的结果，外显率不完全，大约有 1,300 年的历史，并且不仅限于犹太人。
Background: Recessively inherited hereditary inclusion body myopathy (HIBM) with quadriceps sparing was initially described only in Jews originating from the region of Persia. The recent identification of the gene responsible for this myopathy and the common "Persian Jewish mutation" (M712T) enabled the re-evaluation of atypical phenotypes and the epidemiology of HIBM in various communities in the Middle East. Objective: To test for the M712T mutation in the DNA from HIBM patients in the Middle East. Methods: DNA from all suspected HIBM patients was tested for the M712T mutation. Unaffected members of families with genetically proven HIBM were studied too. In the majority of families, haplotype construction with markers spanning the 700-kb region of the HIBM gene was performed. Results: One hundred twenty-nine HIBM patients of 55 families (Middle Eastern Jews, Karaites, and Arab Muslims of Palestinian and Bedouin origin) were homozygous for the M712T mutation, and all carried the same haplotype. Five clinically unaffected subjects were also homozygous for the common mutation and haplotype, including two older adults (ages 50 and 68 years). Atypical features with this same mutation were marked quadriceps weakness in five patients, proximal weakness only in two patients, facial weakness in three patients, and a muscle biopsy showing perivascular inflammation in one patient. Conclusions: The phenotypic spectrum of recessive HIBM is wider than previously described, and the diagnostic criteria for this myopathy must be changed. The Middle Eastern cluster is the result of a founder mutation, with incomplete penetrance, that is approximately 1,300 years old and is not limited to Jews.