A new locus (SPG46) maps to 9p21.2-q21.12 in a Tunisian family with a complicated autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum.

Amir Boukhris, Imed Feki, Nizar Elleuch, Mohamed Imed Miladi, Anne Boland-Augé, Jérémy Truchetto, Emeline Mundwiller, Nadia Jezequel, Diana Zelenika, Chokri Mhiri, Alexis Brice, Giovanni Stevanin
Neurogenetics. 2010-07-01; 11(4): 441-448
DOI: 10.1007/s10048-010-0249-2

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1. Neurogenetics. 2010 Oct;11(4):441-8. doi: 10.1007/s10048-010-0249-2. Epub 2010
Jul 1.

A new locus (SPG46) maps to 9p21.2-q21.12 in a Tunisian family with a complicated
autosomal recessive hereditary spastic paraplegia with mental impairment and thin
corpus callosum.

Boukhris A(1), Feki I, Elleuch N, Miladi MI, Boland-Augé A, Truchetto J,
Mundwiller E, Jezequel N, Zelenika D, Mhiri C, Brice A, Stevanin G.

Author information:
(1)Department of Neurology, Habib Bourguiba University Hospital, Sfax, Tunisia.

Hereditary spastic paraplegia (HSP) with thin corpus callosum (TCC) and mental
impairment is a frequent subtype of complicated HSP, often inherited as an
autosomal recessive (AR) trait. It is clear from molecular genetic analyses that
there are several underlying causes of this syndrome, with at least six genetic
loci identified to date. However, SPG11 and SPG15 are the two major genes for
this entity. To map the responsible gene in a large AR-HSP-TCC family of Tunisian
origin, we investigated a consanguineous family with a diagnosis of AR-HSP-TCC
excluded for linkage to the SPG7, SPG11, SPG15, SPG18, SPG21, and SPG32 loci. A
genome-wide scan was undertaken using 6,090 SNP markers covering all chromosomes.
The phenotypic presentation in five patients was suggestive of a complex HSP that
associated an early-onset spastic paraplegia with mild handicap, mental
deterioration, congenital cataract, cerebellar signs, and TCC. The genome-wide
search identified a single candidate region on chromosome 9, exceeding the LOD
score threshold of +3. Fine mapping using additional markers narrowed the
candidate region to a 45.1-Mb interval (15.4 cM). Mutations in three candidate
genes were excluded. The mapping of a novel AR-HSP-TCC locus further demonstrates
the extensive genetic heterogeneity of this condition. We propose that testing
for this locus should be performed, after exclusion of mutations in SPG11 and
SPG15 genes, in AR-HSP-TCC families, especially when cerebellar ataxia and
cataract are present.

DOI: 10.1007/s10048-010-0249-2
PMID: 20593214 [Indexed for MEDLINE]

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