A refined physical and transcriptional map of the SPG9 locus on 10q23.3–q24.2

Abstract

Hereditary spastic paraplegia (HSP) is a genetically heterogeneous disorder characterised by progressive spasticity of the lower limbs. Beside 'pure' forms of HSP, 'complicated' forms are reported, where spasticity occurs associated with additional symptoms. We recently described an Italian family with a complicated dominant form of HSP (SPG9) and we mapped the gene responsible to 10q23.3-q24.2, in a 12 cM interval between markers D10S564 and D10S603. The phenotypic manifestations in our family are reminiscent of those already described in a smaller British pedigree. We typed individuals from this British family using markers located in the SPG9 critical interval and haplotype reconstruction showed the disorder co-segregating with SPG9. To characterise the SPG9 region better, we constructed a contig of 22 YACs, assigned it to 18 polymorphic markers and positioned 54 ESTs. Furthermore, we searched for ESTs containing a trinucleotide repeat sequence, since anticipation of symptoms was reported in both families. Finally, analysis of a muscle biopsy specimen from one patient was normal, suggesting that, contrary to SPG7, mitochondrial disturbance could not be a primary feature of SPG9.

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

“…Aetiology: the mutated gene has not yet been detected but linkage analysis located the mutated gene to chromosome 10q23.3-24.1 [69].…”

“…Clinical presentation: SPG9 represents a complex SPG with cataracts, gastro-esophageal reflux, and motor PNP in addition to "pure" manifestations [69].…”

A novel locus for pure recessive hereditary spastic paraplegia maps to 10q22.1‐10q24.1

“…10 It has been suggested that the syndrome described in the two families is genetically homogeneous. 9 Furthermore, a family with HSP and epilepsy was excluded for linkage to the SPG9 locus, which overlapped a partial epilepsy locus.…”

“…8 The critical disease interval of 12cM (Ϸ9.2Mb) was slightly refined to approximately 7Mb when a second family with a motor system disorder linked to the SPG9 locus. 8,9 In addition to the motor system feature, this British family presented with bilateral cataracts, short stature, learning difficulties, muscle weakness, skeletal abnormalities, and anticipation. 10 It has been suggested that the syndrome described in the two families is genetically homogeneous.…”

“…10 It has been suggested that the syndrome described in the two families is genetically homogeneous. 9 Furthermore, a family with HSP and epilepsy was excluded for linkage to the SPG9 locus, which overlapped a partial epilepsy locus. 11 In this study, we present a large single-generation French Canadian family with pure recessive HSP for which we have mapped the disease locus, SPG27, to chromosome 10q22.1-10q24.1 by linkage analysis.…”