Refinement of the SPG15 candidate interval and phenotypic heterogeneity in three large Arab families.

Nizar Elleuch, Naima Bouslam, Sylvain Hanein, Alexander Lossos, Abdelmadjid Hamri, Stephan Klebe, Vardiella Meiner, Nezha Birouk, Israela Lerer, Djamel Grid, Delphine Bacq, Meriem Tazir, Diana Zelenika, Zohar Argov, Alexandra Durr, Mohamed Yahyaoui, Ali Benomar, Alexis Brice, Giovanni Stevanin
Neurogenetics. 2007-07-28; 8(4): 307-315
DOI: 10.1007/s10048-007-0097-x

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1. Neurogenetics. 2007 Nov;8(4):307-15. Epub 2007 Jul 28.

Refinement of the SPG15 candidate interval and phenotypic heterogeneity in three
large Arab families.

Elleuch N(1), Bouslam N, Hanein S, Lossos A, Hamri A, Klebe S, Meiner V, Birouk
N, Lerer I, Grid D, Bacq D, Tazir M, Zelenika D, Argov Z, Durr A, Yahyaoui M,
Benomar A, Brice A, Stevanin G.

Author information:
(1)INSERM, U679, Groupe Hospitalier Pitié-Salpêtrière, 47 Bd de l’Hôpital, 75013
Paris, France.

Hereditary spastic paraplegia (HSP) type 15 is an autosomal recessive (AR) form
of complicated HSP mainly characterized by slowly progressive spastic paraplegia,
mental retardation, intellectual deterioration, maculopathy, distal amyotrophy,
and mild cerebellar signs that has been associated with the Kjellin syndrome. The
locus for this form of HSP, designated SPG15, was mapped to an interval of 19 cM
on chromosome 14q22-q24 in two Irish families. We performed a clinical-genetic
study of this form of HSP on 147 individuals (64 of whom were affected) from 20
families with AR-HSP. A genome-wide scan was performed in three large
consanguineous families of Arab origin after exclusion of linkage to several
known loci for AR-HSP (SPG5, SPG7, SPG21, SPG24, SPG28, and SPG30). The 17 other
AR-HSP families were tested for linkage to the SPG15 locus. Only the three large
consanguineous families showed evidence of linkage to the SPG15 locus (2.4 > Z
(max) > 4.3). Recombinations in these families reduced the candidate region from
approximately 16 to approximately 5 Mbases. Among the approximately 50 genes
assigned to this locus, two were good candidates by their functions (GPHN and
SLC8A3), but their coding exons and untranslated regions (UTRs) were excluded by
direct sequencing. Patients had spastic paraplegia associated with cognitive
impairment, mild cerebellar signs, and axonal neuropathy, as well as a thin
corpus callosum in one family. The ages at onset ranged from 10 to 19 years. Our
study highlights the phenotypic heterogeneity of SPG15 in which mental
retardation or cognitive deterioration, but not all other signs of Kjellin
syndrome, are associated with HSP and significantly reduces the SPG15 locus.

DOI: 10.1007/s10048-007-0097-x
PMID: 17661097 [Indexed for MEDLINE]

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