Spectrum and detection rate of L1CAM mutations in isolated and familial cases with clinically suspected L1-disease.
Am J Med Genet
; 92(1): 40-6, 2000 May 01.
Article
in En
| MEDLINE
| ID: mdl-10797421
ABSTRACT
Mutations in L1CAM, the gene encoding the L1 neuronal cell adhesion molecule, lead to an X-linked trait characterized by one or more of the symptoms of hydrocephalus, adducted thumbs, agenesis or hypoplasia of corpus callosum, spastic paraplegia, and mental retardation (L1-disease). We screened 153 cases with prenatally or clinically suspected X-chromosomal hydrocephalus for L1CAM mutations by SSCP analysis of the 28 coding exons and regulatory elements in the 5'-untranslated region of the gene. Forty-six pathogenic mutations were found (30.1% detection rate), the majority consisting of nonsense, frameshift, and splice site mutations. In eight cases, segregation analysis disclosed recent de novo mutations. Statistical analysis of the data indicates a significant effect on mutation detection rate of (i) family history, (ii) number of L1-disease typical clinical findings, and (iii) presence or absence of signs not typically associated with L1CAM-disease. Whereas mutation detection rate was 74.2% for patients with at least two additional cases in the family, only 16 mutations were found in the 102 cases with negative family history (15.7% detection rate). Our data suggest a higher than previously assumed contribution of L1CAM mutations in the pathogenesis of the heterogeneous group of congenital hydrocephalus.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
X Chromosome
/
Abnormalities, Multiple
/
Membrane Glycoproteins
/
Neural Cell Adhesion Molecules
Type of study:
Diagnostic_studies
Language:
En
Journal:
Am J Med Genet
Year:
2000
Document type:
Article
Affiliation country:
Germany