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LIS1 and XLIS (DCX) mutations cause most classical lissencephaly, but different patterns of malformation.
- Source :
-
Human molecular genetics [Hum Mol Genet] 1998 Dec; Vol. 7 (13), pp. 2029-37. - Publication Year :
- 1998
-
Abstract
- Classical lissencephaly (LIS) is a neuronal migration disorder resulting in brain malformation, epilepsy and mental retardation. Deletions or mutations of LIS1 on 17p13.3 and mutations in XLIS ( DCX ) on Xq22.3-q23 produce LIS. Direct DNA sequencing of LIS1 and XLIS was performed in 25 children with sporadic LIS and no deletion of LIS1 by fluorescence in situ hybridization. Mutations of LIS1 were found by sequencing ( n = 8) and Southern blot ( n = 2) in a total of 10 patients (40%) of both sexes and mutations of XLIS in five males (20%). Combined with previous data, deletions or mutations of these two genes account for approximately 76% of isolated LIS. These data demonstrate that LIS1 and XLIS mutations cause the majority of, though not all, human LIS. The mutations in LIS1 were predicted to result in protein truncation in six of eight patients and splice site mutations in two, all of which disrupt one or more of the seven WD40 repeats contained in the LIS1 protein. Point mutations in XLIS identified the C-terminal serine/proline-rich region as potentially important for protein function. The patients with mutations were included in a genotype-phenotype analysis of 32 subjects with deletions or other mutations of these two genes. Whereas the brain malformation due to LIS1 mutations was more severe over the parietal and occipital regions, XLIS mutations produced the reverse gradient, which was more severe over the frontal cortex. The distinct LIS patterns suggest that LIS1 and XLIS may be part of overlapping, but distinct, signaling pathways that promote neuronal migration.
- Subjects :
- 1-Alkyl-2-acetylglycerophosphocholine Esterase
Amino Acid Sequence
Brain pathology
DNA chemistry
DNA genetics
DNA Mutational Analysis
Doublecortin Domain Proteins
Doublecortin Protein
Exons
Female
Genotype
Humans
Intellectual Disability genetics
Intellectual Disability pathology
Introns
Male
Molecular Sequence Data
Mutation
Nervous System Malformations pathology
Phenotype
Brain abnormalities
Microtubule-Associated Proteins
Nervous System Malformations genetics
Neuropeptides genetics
Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0964-6906
- Volume :
- 7
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Human molecular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 9817918
- Full Text :
- https://doi.org/10.1093/hmg/7.13.2029