title: A new phenotype linked to SPG27 and refinement of the critical region on chromosome.
abstract: Hereditary spastic paraplegias are genetically and clinically heterogeneous. Twenty-six loci have been identified to date. SPG27 was recently mapped to chromosome 10 in a single family with autosomal recessive hereditary spastic paraplegia (AR-HSP) and a pure phenotype. We describe a Tunisian family with a complicated form of AR-HSP also linked to SPG27. The parents are first cousins and 3 out of their 4 children manifest early onset progressive spastic paraparesis associated with sensorimotor polyneuropathy. In addition, the eldest girl had facial dysmorphism and short stature (-3SD). Two of the three patients were mentally retarded, and one of these also had cerebellar signs. Their ages at onset were 2, 5 and 7 years. A genome-wide scan suggested linkage to SPG27 on the long arm of chromosome 10 with a multipoint lod score of 2.54. In addition, a recombination detected in this family by haplotype reconstruction reduced the SPG27 locus from 25 to 19.6 cM. This is the first clinical description of a complicated form of spastic paraplegia, characterized by great phenotypic variability among the sibs, associated with the SPG27 locus.
authors.affiliation: INSERM U679 (former U289), Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Ribai
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
authors.forename: Naima
authors.initials: N
authors.lastname: Bouslam
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Pontier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Nelson
authors.forename: Bertrand
authors.initials: B
authors.lastname: Fontaine
authors.forename: Christel
authors.initials: C
authors.lastname: Dussert
authors.forename: Céline
authors.initials: C
authors.lastname: Charon
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000473:pathology*; D002874:Chromosome Mapping / Q000379:methods; D002879:Chromosomes, Human, Pair 10; D005192:Family Health; D005260:Female; D006801:Humans; D008126:Lod Score; D008279:Magnetic Resonance Imaging; D008297:Male; D010641:Phenotype; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000473:pathology*