A novel locus for autosomal dominant « uncomplicated » hereditary spastic paraplegia maps to chromosome 8p21.1-q13.3.
Hum Genet. 2007-06-28; 122(3-4): 261-273
DOI: 10.1007/s00439-007-0396-1
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1. Hum Genet. 2007 Nov;122(3-4):261-73. Epub 2007 Jun 28.
A novel locus for autosomal dominant « uncomplicated » hereditary spastic
paraplegia maps to chromosome 8p21.1-q13.3.
Hanein S(1), Dürr A, Ribai P, Forlani S, Leutenegger AL, Nelson I, Babron MC,
Elleuch N, Depienne C, Charon C, Brice A, Stevanin G.
Author information:
(1)INSERM, Unit 679, 47 Bd de l’Hôpital, 75013 Paris, France.
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.
DOI: 10.1007/s00439-007-0396-1
PMID: 17605047 [Indexed for MEDLINE]