Abstract
Cerebral palsy has an incidence of approximately 1/500 births, although this varies between different ethnic groups. Genetic forms of the disease account for approximately 1%-2% of cases in most countries but contribute a larger proportion in populations with extensive inbreeding. We have clinically characterized consanguineous families with multiple children affected by symmetrical spastic cerebral palsy, to locate recessive genes responsible for this condition. The eight families studied were identified from databases of patients in different regions of the United Kingdom. After ascertainment and clinical assessment, we performed a genomewide search for linkage, using 290 polymorphic DNA markers. In three families, a region of homozygosity at chromosome 2q24-q25 was identified between the markers D2S124 and D2S148. The largest family gave a maximum LOD score of 3.0, by multipoint analysis (HOMOZ). The maximum combined multipoint LOD score for the three families was 5.75. The minimum region of homozygosity is approximately 5 cM between the markers D2S124 and D2S2284. We have shown that a proportion of autosomal recessive symmetrical spastic cerebral palsy maps to chromosome 2q24-25. The identification of genes involved in the etiology of cerebral palsy may lead to improved management of this clinically intractable condition.
Full Text
The Full Text of this article is available as a PDF (246.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Blair E., Stanley F. J. Intrapartum asphyxia: a rare cause of cerebral palsy. J Pediatr. 1988 Apr;112(4):515–519. doi: 10.1016/s0022-3476(88)80161-6. [DOI] [PubMed] [Google Scholar]
- Bundey S., Alam H. A five-year prospective study of the health of children in different ethnic groups, with particular reference to the effect of inbreeding. Eur J Hum Genet. 1993;1(3):206–219. doi: 10.1159/000472414. [DOI] [PubMed] [Google Scholar]
- Bundey S., Griffiths M. I. Recurrence risks in families of children with symmetrical spasticity. Dev Med Child Neurol. 1977 Apr;19(2):179–191. doi: 10.1111/j.1469-8749.1977.tb07968.x. [DOI] [PubMed] [Google Scholar]
- Bundey S., Griffiths M. I., Young J. A. Recurrence risk of symmetrical spastic cerebral palsy. Dev Med Child Neurol. 1978 Jun;20(3):390–391. doi: 10.1111/j.1469-8749.1978.tb15233.x. [DOI] [PubMed] [Google Scholar]
- Gustavson K. H., Hagberg B., Sanner G. Identical syndromes of cerebral palsy in the same family. Acta Paediatr Scand. 1969 Jul;58(4):330–340. doi: 10.1111/j.1651-2227.1969.tb04729.x. [DOI] [PubMed] [Google Scholar]
- Hagberg B., Sanner G., Steen M. The dysequilibrium syndrome in cerebral palsy. Clinical aspects and treatment. Acta Paediatr Scand Suppl. 1972;226:1–63. [PubMed] [Google Scholar]
- Hughes I., Newton R. Genetic aspects of cerebral palsy. Dev Med Child Neurol. 1992 Jan;34(1):80–86. doi: 10.1111/j.1469-8749.1992.tb08568.x. [DOI] [PubMed] [Google Scholar]
- Kruglyak L., Daly M. J., Lander E. S. Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping. Am J Hum Genet. 1995 Feb;56(2):519–527. [PMC free article] [PubMed] [Google Scholar]
- Mitchell S., Bundey S. Symmetry of neurological signs in Pakistani patients with probable inherited spastic cerebral palsy. Clin Genet. 1997 Jan;51(1):7–14. doi: 10.1111/j.1399-0004.1997.tb02406.x. [DOI] [PubMed] [Google Scholar]
- Ott J. A computer program for linkage analysis of general human pedigrees. Am J Hum Genet. 1976 Sep;28(5):528–529. [PMC free article] [PubMed] [Google Scholar]
- Pharoah P. O., Cooke T., Rosenbloom I., Cooke R. W. Trends in birth prevalence of cerebral palsy. Arch Dis Child. 1987 Apr;62(4):379–384. doi: 10.1136/adc.62.4.379. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reed P. W., Davies J. L., Copeman J. B., Bennett S. T., Palmer S. M., Pritchard L. E., Gough S. C., Kawaguchi Y., Cordell H. J., Balfour K. M. Chromosome-specific microsatellite sets for fluorescence-based, semi-automated genome mapping. Nat Genet. 1994 Jul;7(3):390–395. doi: 10.1038/ng0794-390. [DOI] [PubMed] [Google Scholar]
- Stanley F. J. The aetiology of cerebral palsy. Early Hum Dev. 1994 Feb;36(2):81–88. doi: 10.1016/0378-3782(94)90035-3. [DOI] [PubMed] [Google Scholar]