Molecular analysis of the Smith-Magenis syndrome: a possible contiguous-gene syndrome associated with del(17)(p11.2).
Molecular analysis of the Smith-Magenis syndrome: a possible contiguous-gene syndrome associated with del(17)(p11.2).
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DOI：
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发表时间：
1991-12
影响因子：
9.8
通讯作者：
F. Greenberg;Guzzetta;R. MontesdeOca-Luna;Magenis Re;Smith Ac;Richter Sf;I. Kondo;W. Dobyns;P. Patel;Lupski
中科院分区：
文献类型：
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作者：
F. Greenberg;Guzzetta;R. MontesdeOca-Luna;Magenis Re;Smith Ac;Richter Sf;I. Kondo;W. Dobyns;P. Patel;Lupski
我们对与17号染色体p11.2带间质缺失相关的Smith-Magenis综合征（SMS）患者进行了临床评估（32例）和分子评估（31例）。患者的周围神经病变的临床和电生理评估，因为标记显示密切联系的一种形式的沙科-玛丽-图斯病（CMT1A）映射到这个染色体区域。常见临床表现为中脸宽平伴头短，鼻梁宽，趾短，言语迟缓，声音沙哑低沉。55%的患者表现出提示周围神经病变的临床症状（例如，深肌腱反射减少或缺失，平足或足弓，对疼痛的敏感性降低，腿部肌肉量减少）。然而，与CMT1A患者不同，这些患者表现出正常的神经传导速度。67%的患者有自毁行为，主要是躁狂和多栓子躁狂，62%的患者有明显的睡眠障碍症状。多导睡眠图显示两例患者缺乏快速眼动睡眠。Southern分析表明，大多数患者的5个17p11.2标记——FG1 （D17S446）、1516 （D17S258）、pYNM67-R5 （D17S29）、pA10-41 （D17S71）和pS6.1-HB2 （D17S445）——被删除，从而确定了一个似乎对SMS至关重要的区域。该缺失在9例患者中被确定为父系起源，在6例患者中被确定为母系起源。在15例患者中记录的明显的随机亲本缺失表明，基因组印迹在SMS临床表型的表达中不起作用。我们的研究结果表明，SMS可能是一种包含特征性临床特征、发育迟缓、周围神经病变临床症状、睡眠功能异常和特定行为异常的连续基因缺失综合征。
We undertook clinical evaluation (32 cases) and molecular evaluation (31 cases) of unrelated patients affected with Smith-Magenis syndrome (SMS) associated with an interstitial deletion of band p11.2 of chromosome 17. Patients were evaluated both clinically and electrophysiologically for peripheral neuropathy, since markers showing close linkage to one form of Charcot-Marie-Tooth disease (CMT1A) map to this chromosomal region. The common clinical findings were broad flat midface with brachycephaly, broad nasal bridge, brachydactyly, speech delay, and hoarse, deep voice. Fifty-five percent of the patients showed clinical signs (e.g., decreased or absent deep tendon reflexes, pes planus or pes cavus, decreased sensitivity to pain, and decreased leg muscle mass) suggestive of peripheral neuropathy. However, unlike patients with CMT1A, these patients demonstrated normal nerve conduction velocities. Self-destructive behaviors, primarily onychotillomania and polyembolokoilamania, were observed in 67% of the patients, and significant symptoms of sleep disturbance were observed in 62%. The absence of REM sleep was demonstrated by polysomnography in two patients. Southern analysis indicated that most patients were deleted for five 17p11.2 markers--FG1 (D17S446), 1516 (D17S258), pYNM67-R5 (D17S29), pA10-41 (D17S71), and pS6.1-HB2 (D17S445)--thus defining a region which appears to be critical to SMS. The deletion was determined to be of paternal origin in nine patients and of maternal origin in six patients. The apparent random parental origin of deletion documented in 15 patients suggests that genomic imprinting does not play a role in the expression of the SMS clinical phenotype. Our findings suggest that SMS is likely a contiguous-gene deletion syndrome which comprises characteristic clinical features, developmental delay, clinical signs of peripheral neuropathy, abnormal sleep function, and specific behavioral anomalies.