A New Locus for Autosomal Recessive Spastic Paraplegia Associated with Mental Retardation and Distal Motor Neuropathy, SPG14, Maps to Chromosome 3q27-q28

Abstract

Hereditary spastic paraplegias (HSPs), a group of neurodegenerative disorders that cause progressive spasticity of the lower limbs, are characterized by clinical and genetic heterogeneity. To date, three loci for autosomal recessive HSP have been mapped on chromosomes 8p, 16q, and 15q. After exclusion of linkage at these loci, we performed a genomewide search in a consanguineous Italian family with autosomal recessive HSP complicated by mild mental retardation and distal motor neuropathy. Using homozygosity mapping, we obtained positive LOD scores for markers on chromosome region 3q27-q28, with a maximum multipoint LOD score of 3.9 for marker D3S1601. Haplotype analysis allowed us to identify a homozygous region (4.5 cM), flanked by markers D3S1580 and D3S3669, that cosegregates with the disease. These data strongly support the presence, on chromosome 3q27-28, of a new locus for complicated recessive spastic paraplegia, which we have named "SPG14."

Hereditary spastic paraplegia: Clinical-genetic characteristics and evolving molecular mechanisms

“…Several other ARHSP loci, namely SPG14 (Vazza et al, 2000), SPG23 (Blumen et al, 2003), SPG24 (Hodgkinson et al, 2002), SPG25 (Zortea et al, 2002), SPG27 (Meijer et al, 2004;Ribaï et al, 2006), SPG32 (Stevanin et al, 2007a), and SPG45 (Dursun et al, 2009), have been identified but pathological genes are yet unknown (Tables 1 and 2). …”

Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance

“…Aetiology: the causative gene has not yet been identified but the mutated gene was mapped to chromosome 3q27-28 (Table 2) [95].…”

Mitochondrial ribosomal proteins: Candidate genes for mitochondrial disease

“…Cardiac disorders for which there may be a mitochondrial involvement are Dilated Cardiomyopathy, Dilated, 1E, 58 and DiGeorge Syndrome. 57 Muscle, nerve, and dementia disorders with mitochondrial involvement include Neuritis with Brachial Predilection, 59 spinocerebellar ataxia, Alzheimer Disease (AD), Parkinson disease, Spastic paraplegia 14, 60 and Vacuolar neuromyopathy. 61 Alzheimer disease and Parkinson disease has been included in our listing because susceptibility to these diseases has been associated with defects in mitochondrial DNA.…”