A new phenotype linked to SPG27 and refinement of the critical region on chromosome.
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.
Ribai
Pascale
P
INSERM U679 (former U289), Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris, France.
Stevanin
Giovanni
G
Bouslam
Naima
N
Pontier
Bénédicte
B
Nelson
Isabelle
I
Fontaine
Bertrand
B
Dussert
Christel
C
Charon
Céline
C
Durr
Alexandra
A
Brice
Alexis
A
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*