New developments in Smith-Magenis syndrome (del 17p11.2)
New developments in Smith-Magenis syndrome (del 17p11.2)
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DOI：
10.1097/wco.0b013e3280895dba
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发表时间：
2007-04-01
影响因子：
4.8
通讯作者：
Smith, Ann C. M.
中科院分区：
文献类型：
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作者：
Gropman, Andrea L.;Elsea, Sarah;Smith, Ann C. M.
综述的目的最近的临床、神经影像学、睡眠和分子I细胞遗传学研究为Smith-Magenis表型的机制提供了新的见解，并在此综述中进行了总结。以及导致昼夜节律紊乱的褪黑激素分泌的倒置模式。一个共同的染色体17p11.2缺失区间跨越约3.5 Mb的染色体缺失的个体中确定约70%。最近报道了Smith-Magenis综合征患者RAI 1基因在Smith-Magenis综合征关键区域内的杂合子点突变，而荧光原位杂交检测不到缺失。RAI 1基因内突变以及缺失的患者共享大多数但不是所有方面的表型.SummaryFindings从分子细胞遗传学分析表明，其他基因或遗传背景可能发挥作用，改变下游效应的RAI 1的功能可用性。对Smith-Magenis综合征关键区域中其他基因的进一步研究将有助于确定它们在改变Smith-Magenis综合征表型的特征或严重程度中所起的作用。需要更多的研究将临床研究的进展转化为新的治疗方案，以解决这种疾病的睡眠和神经行为问题。
Purpose of reviewRecent clinical, neuroimaging, sleep, and molecular I cytogenetic studies have provided new insights into the mechanisms leading to the Smith-Magenis phenotype and are summarized in this review.Recent findingsCross sectional studies of patients with Smith-Magenis syndrome have found evidence for central and peripheral nervous system abnormalities, neurobehavioral disturbances, and an inverted pattern of melatonin secretion leading to circadian rhythm disturbance. A common chromosome 17p11.2 deletion interval spanning approximately 3.5 Mb is identified in about 70% of individuals with chromosome deletion. Recently heterozygous point mutations in the RAI1 gene within the Smith-Magenis syndrome critical region have been reported in Smith-Magenis syndrome patients without detectable deletion by fluorescent in-situ hybridization. Patients with intragenic mutations in RAI1 as well as those with deletions share most but not all aspects of the phenotype.SummaryFindings from molecular cytogenetic analysis suggest that other genes or genetic background may play a role in altering the functional availability of RAI1 for downstream effects. Further research into additional genes in the Smith-Magenis syndrome critical region will help define the role they play in modifying features or severity of the Smith-Magenis syndrome phenotype. More research is needed to translate advances in clinical research into new treatment options to address the sleep and neurobehavioral problems in this disorder.