Clinical features and molecular analysis of the alpha thalassemia/mental retardation syndromes. II. Cases without detectable abnormality of the alpha globin complex.
Clinical features and molecular analysis of the alpha thalassemia/mental retardation syndromes. II. Cases without detectable abnormality of the alpha globin complex.
复制标题
α地中海贫血/智力低下综合征的临床特征和分子分析。
DOI：
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发表时间：
1990
影响因子：
9.8
通讯作者：
D. R. Higgs
中科院分区：
文献类型：
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作者：
Andrew ONI Wilkie;H. Zeitlin;R. Lindenbaum;V. Buckle;N. Fischel‐Ghodsian;David H.K. Chui;D. Gardner‐medwin;M. Macgillivray;D. Weatherall;D. R. Higgs
我们已经确定了五个无关的病人，所有的北欧血统，谁有血红蛋白H（Hb H）的疾病和深刻的精神障碍。令人惊讶的是，α珠蛋白复合物的详细分子分析在这些受试者中是正常的。在临床上，他们表现出相当一致的异常，特别是严重的精神障碍，小头畸形，相对距离过远，不寻常的面容和生殖器异常。从血液学上讲，他们的Hb H疾病比公认的孟德尔疾病形式具有微妙但明显温和的性质。这些共同的特征表明，这五个“非缺失”患者有一个类似的潜在突变，与所附论文中描述的与α地中海贫血和轻度至中度智力低下相关的16p13.3缺失完全不同。我们推测，这个潜在的突变位点是不密切相关的α珠蛋白复合物，并可能编码一个反式作用因子参与α珠蛋白表达的正常调节。
We have identified five unrelated patients, all of north European origin, who have hemoglobin H (Hb H) disease and profound mental handicap. Surprisingly, detailed molecular analysis of the alpha globin complex is normal in these subjects. Clinically, they present with a rather uniform constellation of abnormalities, notably severe mental handicap, microcephaly, relative hypertelorism, unusual facies and genital anomalies. Hematologically, their Hb H disease has subtly but distinctly milder properties than the recognized Mendelian forms of the disease. These common features suggest that these five "nondeletion" patients have a similar underlying mutation, quite distinct from the 16p13.3 deletion associated with alpha thalassemia and mild to moderate mental retardation described in the accompanying paper. We speculate that the locus of this underlying mutation is not closely linked to the alpha globin complex and may encode a trans-acting factor involved in the normal regulation of alpha globin expression.