Uyanik, G. and Morris-Rosendahl, D. J. and Stiegler, J. and Klapecki, J. and Gross, C. and Berman, Y. and Martin, P. and Dey, L. and Spranger, S. and Korenke, G. C. and Schreyer, I. and Hertzberg, C. and Neumann, T. E. and Burkart, P. and Spaich, C. and Meng, N. and Holthausen, H. and Ades, L. and Seidel, J. and Mangold, E. and Buyse, G. and Meinecke, P. and Schara, U. and Zeschnigk, C. and Muller, D. and Helland, G. and Schulze, B. and Wright, M. L. and Kortge-Jung, S. and Hehr, A. and Bogdahn, U. and Schuierer, G. and Kohlhase, J. and Aigner, L. and Wolff, G. and Hehr, U. and Winkler, J. (2007) Location and type of mutation in the LIS1 gene do not predict phenotypic severity. NEUROLOGY, 69 (5). pp. 442-447. ISSN 0028-3878,
Full text not available from this repository. (Request a copy)Abstract
Background: Lissencephaly is a neuronal migration disorder leading to absent or reduced gyration and a broadened but poorly organized cortex. The most common form of lissencephaly is isolated, referred as classic or type 1 lissencephaly. Type 1 lissencephaly is mostly associated with a heterozygous deletion of the entire LIS1 gene, whereas intragenic heterozygous LIS1 mutations or hemizygous DCX mutations in males are less common. Methods: Eighteen unrelated patients with type 1 lissencephaly were clinically and genetically assessed. In addition, patients with subcortical band heterotopia (n = 1) or lissencephaly with cerebellar hypoplasia (n = 2) were included. Results: Fourteen new and seven previously described LIS1 mutations were identified. We observed nine truncating mutations (nonsense, n = 2; frameshift, n = 7), six splice site mutations, five missense mutations, and one in-frame deletion. Somatic mosaicism was assumed in three patients with partial subcortical band heterotopia in the occipital-parietal lobes or mild pachygyria. We report three mutations in exon 11, including a frameshift which extends the LIS1 protein, leading to type 1 lissencephaly and illustrating the functional importance of the WD domains at the C terminus. Furthermore, we present two patients with novel LIS1 mutations in exon 10 associated with lissencephaly with cerebellar hypoplasia type a. Conclusion: In contrast to previous reports, our data suggest that neither type nor position of intragenic mutations in the LIS1 gene allows an unambiguous prediction of the phenotypic severity. Furthermore, patients presenting with mild cerebral malformations such as subcortical band heterotopia or cerebellar hypoplasia should be considered for genetic analysis of the LIS1 gene.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SUBCORTICAL BAND HETEROTOPIA; ISOLATED LISSENCEPHALY SEQUENCE; MISSENSE MUTATIONS; DIEKER-SYNDROME; ACETYLHYDROLASE; MALFORMATION; MIGRATION; MALES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Dec 2020 10:23 |
| Last Modified: | 02 Dec 2020 10:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32493 |
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