Both pure and complicated forms found
An in-depth study of 175 French HSPers with mutations in REEP1 (SPG31) has found both pure and complicated forms of HSP.
Hereditary spastic paraplegias (HSP) constitute a heterogeneous group of neurodegenerative disorders characterized at least by slowly progressive spasticity of the lower limbs. Mutations in REEP1 were recently associated with a pure dominant HSP, SPG31.
We sequenced all exons of REEP1 and searched for rearrangements by MLPA in a large panel of 175 unrelated HSP index patients from kindreds with dominant inheritance (AD-HSP), with either pure (n=102) or complicated (n=73) forms of the disease, after exclusion of other known HSP genes.
We identified 12 different heterozygous mutations, including two exon deletions, associated with either a pure or a complex phenotype. The overall mutation rate in our clinically heterogeneous sample was 4.5% in French families with AD-HSP. The phenotype was restricted to pyramidal signs in the lower limbs in most patients but 9 had a complex phenotype associating axonal peripheral neuropathy (=5/11 patients) including a Silver-like syndrome in one patient, and less frequently cerebellar ataxia, tremor, dementia. Interestingly, we evidenced abnormal mitochondrial network organization in fibroblasts of one patient in addition to defective mitochondrial energy production in both fibroblasts and muscle, but whether these anomalies are directly or indirectly related to the mutations remains uncertain.
SOURCE: Hum Mutat. 2011 May 26. doi: 10.1002/humu.21542. [Epub ahead of print]
REEP1 mutations in SPG31: frequency, mutational spectrum and potential association with mitochondrial morpho-functional dysfunction.
Goizet C, Depienne C, Benard G, Boukhris A, Mundwiller E, Solé G, Coupry I, Pilliod J, Martin-Négrier ML, Fedirko E, Forlani S, Cazeneuve C, Hannequin D, Charles P, Feki I, Pinel JF, Ouvrard-Hernandez AM, Lyonnet S, Ollagnon-Roman E, Yaouanq J, Toutain A, Dussert C, Fontaine B, Leguern E, Lacombe D, Durr A, Rossignol R, Brice A, Stevanin G.
Université Bordeaux Segalen, Laboratoire Maladies Rares: Génétique et Métabolisme (MRGM), EA4576, 33076 Bordeaux, France; INSERM, U975, 75013 Paris, France; Université Pierre et Marie Curie – Paris 6, UMR_S975, Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière, GHU Pitié-Salpêtrière, 75013 Paris, France; CNRS, UMR7225, 75013 Paris, France; CHU Bordeaux, Service de Génétique Médicale, 33076 Bordeaux, France.