A New Locus for Autosomal Recessive Hereditary Spastic Paraplegia Maps to Chromosome 16q24.3

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 1998 Jun 23

PMID 9634528

Citations 30

Authors

G De Michele

M De Fusco

F Cavalcanti

A Filla

R Marconi

G Volpe

A Monticelli

A Ballabio

G Casari

S Cocozza

Affiliations

Soon will be listed here.

Abstract

Hereditary spastic paraplegia is a genetically and phenotypically heterogeneous disorder. Both pure and complicated forms have been described, with autosomal dominant, autosomal recessive, and X-linked inheritance. Various loci (SPG1-SPG6) associated with this disorder have been mapped. Here, we report linkage analysis of a large consanguineous family affected with autosomal recessive spastic paraplegia with age at onset of 25-42 years. Linkage analysis of this family excluded all previously described spastic paraplegia loci. A genomewide linkage analysis showed evidence of linkage to chromosome 16q24.3, with markers D16S413 (maximum LOD score 3.37 at recombination fraction [theta] of .00) and D16S303 (maximum LOD score 3.74 at straight theta=.00). Multipoint analysis localized the disease gene in the most telomeric region, with a LOD score of 4.2. These data indicate the presence of a new locus linked to pure recessive spastic paraplegia, on chromosome 16q24.3, within a candidate region of 6 cM.

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References

Harding A . Hereditary "pure" spastic paraplegia: a clinical and genetic study of 22 families. J Neurol Neurosurg Psychiatry. 1981; 44(10):871-83. PMC: 491171. DOI: 10.1136/jnnp.44.10.871. View

Bird T, Cambi F, Dube M, Figlewicz D, Fink J, Haines J . Hereditary spastic paraplegia: advances in genetic research. Hereditary Spastic Paraplegia Working group. Neurology. 1996; 46(6):1507-14. DOI: 10.1212/wnl.46.6.1507. View

Miller S, Dykes D, Polesky H . A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3):1215. PMC: 334765. DOI: 10.1093/nar/16.3.1215. View

Ott J . Computer-simulation methods in human linkage analysis. Proc Natl Acad Sci U S A. 1989; 86(11):4175-8. PMC: 287412. DOI: 10.1073/pnas.86.11.4175. View

Gencic S, Abuelo D, AMBLER M, Hudson L . Pelizaeus-Merzbacher disease: an X-linked neurologic disorder of myelin metabolism with a novel mutation in the gene encoding proteolipid protein. Am J Hum Genet. 1989; 45(3):435-42. PMC: 1683421. View

Pullman W, Bodmer W . Cloning and characterization of a gene that regulates cell adhesion. Nature. 1992; 356(6369):529-32. DOI: 10.1038/356529a0. View

Filla A, De Michele G, Marconi R, Bucci L, Carillo C, Castellano A . Prevalence of hereditary ataxias and spastic paraplegias in Molise, a region of Italy. J Neurol. 1992; 239(6):351-3. DOI: 10.1007/BF00867594. View

Mountjoy K, Robbins L, Mortrud M, Cone R . The cloning of a family of genes that encode the melanocortin receptors. Science. 1992; 257(5074):1248-51. DOI: 10.1126/science.1325670. View

Polo J, Calleja J, Combarros O, Berciano J . Hereditary "pure" spastic paraplegia: a study of nine families. J Neurol Neurosurg Psychiatry. 1993; 56(2):175-81. PMC: 1014818. DOI: 10.1136/jnnp.56.2.175. View

10.

Hazan J, Lamy C, Melki J, Munnich A, De Recondo J, Weissenbach J . Autosomal dominant familial spastic paraplegia is genetically heterogeneous and one locus maps to chromosome 14q. Nat Genet. 1993; 5(2):163-7. DOI: 10.1038/ng1093-163. View

11.

Saugier-Veber P, Munnich A, Bonneau D, Rozet J, Le Merrer M, Gil R . X-linked spastic paraplegia and Pelizaeus-Merzbacher disease are allelic disorders at the proteolipid protein locus. Nat Genet. 1994; 6(3):257-62. DOI: 10.1038/ng0394-257. View

12.

Durr A, Brice A, Serdaru M, RANCUREL G, Derouesne C, Lyon-Caen O . The phenotype of "pure" autosomal dominant spastic paraplegia. Neurology. 1994; 44(7):1274-7. DOI: 10.1212/wnl.44.7.1274. View

13.

Gyapay G, Morissette J, Vignal A, Dib C, Fizames C, Millasseau P . The 1993-94 Généthon human genetic linkage map. Nat Genet. 1994; 7(2 Spec No):246-339. DOI: 10.1038/ng0694supp-246. View

14.

Kobayashi H, Hoffman E, Marks H . The rumpshaker mutation in spastic paraplegia. Nat Genet. 1994; 7(3):351-2. DOI: 10.1038/ng0794-351. View

15.

Jouet M, Rosenthal A, Armstrong G, MacFarlane J, Stevenson R, Paterson J . X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene. Nat Genet. 1994; 7(3):402-7. DOI: 10.1038/ng0794-402. View

16.

Hentati A, Pericak-Vance M, Hung W, Belal S, Laing N, Boustany R . Linkage of 'pure' autosomal recessive familial spastic paraplegia to chromosome 8 markers and evidence of genetic locus heterogeneity. Hum Mol Genet. 1994; 3(8):1263-7. DOI: 10.1093/hmg/3.8.1263. View

17.

Fink J, Wu C, Jones S, Sharp G, Lange B, Lesicki A . Autosomal dominant familial spastic paraplegia: tight linkage to chromosome 15q. Am J Hum Genet. 1995; 56(1):188-92. PMC: 1801321. View

18.

Hazan J, Fontaine B, Bruyn R, Lamy C, van Deutekom J, Rime C . Linkage of a new locus for autosomal dominant familial spastic paraplegia to chromosome 2p. Hum Mol Genet. 1994; 3(9):1569-73. DOI: 10.1093/hmg/3.9.1569. View

19.

Hentati A, Pericak-Vance M, Lennon F, Wasserman B, Hentati F, Juneja T . Linkage of a locus for autosomal dominant familial spastic paraplegia to chromosome 2p markers. Hum Mol Genet. 1994; 3(10):1867-71. DOI: 10.1093/hmg/3.10.1867. View

20.

Dib C, Faure S, Fizames C, Samson D, Drouot N, Vignal A . A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996; 380(6570):152-4. DOI: 10.1038/380152a0. View