Document Detail


Refinement of the SPG15 candidate interval and phenotypic heterogeneity in three large Arab families.
MedLine Citation:
PMID:  17661097     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
12210347 - Familial axenfeld-rieger anomaly, cardiac malformations, and sensorineural hearing loss...
16272057 - Posterior polar cataract: genetic analysis of a large family.
15286787 - Mutations in slc6a19, encoding b0at1, cause hartnup disorder.
1815167 - Dna diagnosis in a family with autosomal dominant aniridia.
3478817 - Regional localization of the gene coding for sphingolipid activator protein sap-1 on hu...
8706027 - Mapping of chromosomal imbalances in pancreatic carcinoma by comparative genomic hybrid...
Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-28
Journal Detail:
Title:  Neurogenetics     Volume:  8     ISSN:  1364-6745     ISO Abbreviation:  Neurogenetics     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-10-23     Completed Date:  2008-04-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9709714     Medline TA:  Neurogenetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  307-15     Citation Subset:  IM    
Affiliation:
INSERM, U679, Groupe Hospitalier Pitié-Salpêtrière, 47 Bd de l'Hôpital, 75013 Paris, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Arabs / genetics
Chromosome Mapping
Chromosomes, Human, Pair 14 / genetics
Consanguinity
Female
Haplotypes
Humans
Male
Microsatellite Repeats
Pedigree
Phenotype
Spastic Paraplegia, Hereditary / genetics*,  psychology
Syndrome

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Systematic study on the mechanism of aldehyde oxidation to carboxylic acid by cytochrome P450.
Next Document:  In vivo mouse spinal cord imaging using echo-planar imaging at 11.75 T.