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]