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A novel locus for autosomal dominant "uncomplicated" hereditary spastic paraplegia maps to chromosome 8p21.1-q13.3.
- Source :
-
Human genetics [Hum Genet] 2007 Nov; Vol. 122 (3-4), pp. 261-73. Date of Electronic Publication: 2007 Jun 28. - Publication Year :
- 2007
-
Abstract
- Hereditary spastic paraplegias (HSPs) are genetically and phenotypically heterogeneous. Both "uncomplicated" and "complicated" forms have been described, with autosomal dominant, autosomal recessive, and X-linked inheritance. Hitherto, ten autosomal dominant "uncomplicated" HSP (ADHSP) loci have been mapped. Here, we report linkage of ADHSP with markers of the 8p21.1-q13.3 chromosomal region in a large French family, including 29 examined at-risk individuals. The age at onset varied from 8 to 60 years with a mean of 31.6 +/- 16.4 years. Multipoint and two-point LOD-score calculations as well as haplotype reconstruction in this region gave support to the location of this novel ADHSP locus (SPG37) in a 43.5 cM genetic interval flanked by loci D8S1839 and D8S1795. The region was shared by all definitely (n = 13), probably (n = 3) and possibly (n = 2) affected patients with a maximum LOD score of 4.20 at the D8S601 locus. Two candidate genes, encoding the kinesin family member 13B and neuregulin 1 (isoforms SMDF and GFF2), were screened for mutations, but no disease-causing alterations were identified. Interestingly, another region, on chromosome 10q22.3-23.31, was found to segregate in all affected patients (but not in probably or possibly affected subjects) and in a high proportion of healthy at risk individuals, suggesting that this locus might act as a modifier of the phenotype.
- Subjects :
- Adolescent
Adult
Age of Onset
Aged
Child
Chromosome Mapping
Chromosomes, Human, Pair 10 genetics
Female
Genetic Markers
Haplotypes
Humans
Kinesins genetics
Lod Score
Male
Microsatellite Repeats
Middle Aged
Nerve Tissue Proteins genetics
Neuregulin-1
Pedigree
Chromosomes, Human, Pair 8 genetics
Genes, Dominant
Spastic Paraplegia, Hereditary genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0340-6717
- Volume :
- 122
- Issue :
- 3-4
- Database :
- MEDLINE
- Journal :
- Human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 17605047
- Full Text :
- https://doi.org/10.1007/s00439-007-0396-1