Autosomal dominant (AD) pure spastic paraplegia (HSP) linked to locus SPG4 affects almost exclusively males in a large pedigree
| Autor: | J Hazan, Mayana Zatz, Sueli K.N. Marie, P Rocco, Maria Rita Passos-Bueno, Alessandra Starling |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Ataxia Spastin Hereditary spastic paraplegia Genetic Linkage DNA Mutational Analysis Locus (genetics) Biology Electronic Letter Genetic linkage Genetics medicine Humans Genetics (clinical) X-linked recessive inheritance Genes Dominant Adenosine Triphosphatases Sex Characteristics Genetic heterogeneity Ichthyosis Spastic Paraplegia Hereditary Haplotype Chromosome Mapping medicine.disease Pedigree Haplotypes Female medicine.symptom Lod Score |
| Zdroj: | Journal of medical genetics. 39(12) |
| ISSN: | 1468-6244 |
| Popis: | Hereditary spastic paraplegia (HSP) includes a heterogeneous group of degenerative disorders of the central motor system characterised by progressive spasticity of the lower limbs. The inheritance may be autosomal dominant (AD), autosomal recessive (AR), or X linked. Clinically, two forms of HSP can be distinguished: a pure form, with leg spasticity and weakness, and a complicated form, with other manifestations such as optic neuropathy, retinopathy, movement disorders, dementia, epilepsy, ataxia, ichthyosis, mental retardation, and deafness. Both complicated and pure forms are genetically heterogeneous. Although X linked forms have been reported,1,2 pure HSP usually displays AD inheritance. The major neuropathological finding in the latter form is axonal degeneration involving the terminal ends of the longest fibres of the corticospinal tracts and dorsal columns.3,4 AD-HSP is the most common form of the disease, accounting for approximately 70-80% of the families. Seven AD loci have been mapped to date: SPG3 on chromosome 14q11.2-q24.3,5,6 SPG4 on chromosome 2p,7,8 SPG6 on chromosome 15q11.1,9 SPG8 on chromosome 8q23-q24,10–13 SPG10 on chromosome 12q13,14 and more recently two novel loci were mapped on chromosome 2q24-q3415 and chromosome 19q13.16 SPG4 is the most common form, accounting for about 40% of all AD-HSP families.17,18 The protein encoded by SPG4, spastin,19 and more recently by SPG3, a GTPAse (SPG3A),20 has just been identified but the gene product of the other AD-HSP forms is still unknown. Here we report a large three generation family referred to us with a diagnosis of pure spastic paraplegia. Pedigree analysis showed the existence of 24 clinically affected males but only one clinically affected female. However, X linked inheritance was ruled out since there were several instances of male to male transmission. Linkage analysis showed that the disease gene … |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|