Dobyns W B, Reiner O, Carrozzo R, Ledbetter D H
Department of Neurology, University of Minnesota Medical School, Minneapolis.
JAMA. 1993 Dec 15;270(23):2838-42. doi: 10.1001/jama.270.23.2838.
We review the clinical phenotype, pathological changes, and results of cytogenetic and molecular genetic studies in 90 probands with lissencephaly (smooth brain) with emphasis on patients with the classical form (type I). We also describe the recent discovery of the lissencephaly gene (LIS1), deletions of which have been implicated as the cause of this disorder in many patients.
We have performed clinical, cytogenetic, and molecular genetic studies of 25 probands with Miller-Dieker syndrome and 65 probands with isolated lissencephaly sequence (ILS). We have further subdivided patients with ILS into those with classical lissencephaly and those with lissencephaly variants.
We consider primarily our own published and unpublished data, but include references to studies of other series of patients with lissencephaly.
Visible cytogenetic deletions of 17p13.3 were detected in 14 of 25 Miller-Dieker syndrome probands, and either visible cytogenetic or submicroscopic deletions in 23 (92%) of 25. Submicroscopic deletions were detected in eight of 45 patients with all types of ILS. If only ILS patients with the classical form are considered, we detected deletions in eight (38%) of 21.
Deletions of the lissencephaly critical region in chromosome 17p13.3, including LIS1, appear to be the most frequent cause of classical lissencephaly. Molecular cytogenetic studies, particularly fluorescence in situ hybridization, should be performed in all such patients. LIS1 shows homology to genes involved in signal transduction, which may be its function in development of the telencephalon. Other genetic causes of classical lissencephaly and genetic and nongenetic causes of other types of lissencephaly exist and are under study.
我们回顾了90例无脑回畸形（平滑脑）先证者的临床表型、病理变化以及细胞遗传学和分子遗传学研究结果，重点关注经典型（I型）患者。我们还描述了无脑回畸形基因（LIS1）的最新发现，该基因的缺失在许多患者中被认为是导致这种疾病的原因。
我们对25例米勒 - 迪克综合征先证者和65例孤立性无脑回序列（ILS）先证者进行了临床、细胞遗传学和分子遗传学研究。我们将ILS患者进一步细分为经典无脑回畸形患者和无脑回畸形变异型患者。
我们主要考虑我们自己已发表和未发表的数据，但也纳入了其他系列无脑回畸形患者研究的参考文献。
在25例米勒 - 迪克综合征先证者中，14例检测到17p13.3可见细胞遗传学缺失，25例中有23例（92%）检测到可见细胞遗传学或亚显微缺失。在45例所有类型ILS患者中，8例检测到亚显微缺失。如果仅考虑经典型的ILS患者，21例中有8例（38%）检测到缺失。
17p13.3染色体上无脑回畸形关键区域（包括LIS1）的缺失似乎是经典无脑回畸形最常见的原因。所有此类患者均应进行分子细胞遗传学研究，尤其是荧光原位杂交。LIS1与参与信号转导的基因具有同源性，这可能是其在端脑发育中的功能。经典无脑回畸形的其他遗传原因以及其他类型无脑回畸形的遗传和非遗传原因存在且正在研究中。
