{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:39:46Z","timestamp":1789990786576,"version":"4.0.1"},"reference-count":18,"publisher":"BMJ","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1993,5]]},"abstract":"<jats:p>X linked hereditary spastic paraplegia is a rare condition that has been divided into two forms (the pure spastic form and the complicated form) as a function of clinical course and severity. A gene for pure hereditary spastic paraplegia (SPG2) has been mapped to the proximal long arm of the X chromosome (Xq21) by linkage to the DXS17 locus, while a gene for a complicated form of the disease has been mapped to the distal long arm by linkage to the DXS52 locus (Xq28). Here we report on the mapping of a gene for complicated hereditary spastic paraplegia to the Xq21 region by linkage to the probe S9 at the DXS17 locus (Z = 5 at theta = 0.04) in a three generation pedigree. Multipoint linkage analysis supports the distal location of the disease gene with respect to the DXYS1-DXS17 block (cen-DXYS1-DXS3-DXS17-SPG2-tel). The observation of a complicated form of spastic paraplegia mapping to Xq21 raises the difficult issue of variable phenotypic expression, allelic heterogeneity, or even close proximity of two genes for hereditary spastic paraplegia in this region. However, since our study provides clinical evidence for intrafamilial heterogeneity in complicated X linked spastic paraplegia, the present data support the hypothesis of variable clinical expression of a single gene at the SPG2 locus, as previously suggested for SPG1. Finally, we report here what we believe to be the first evidence of clinical expression in heterozygous carriers, a feature that is relevant to genetic counselling in at risk females.<\/jats:p>","DOI":"10.1136\/jmg.30.5.381","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:23:16Z","timestamp":1226330596000},"page":"381-384","source":"Crossref","is-referenced-by-count":35,"title":["X linked spastic paraplegia (SPG2): clinical heterogeneity at a single gene locus."],"prefix":"10.1136","volume":"30","author":[{"given":"D","family":"Bonneau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J M","family":"Rozet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Bulteau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Berthier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Mettey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Gil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Munnich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Le Merrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1993,5,1]]},"reference":[{"key":"ref_1","article-title":"Born at 30 weeks' gestation, At 1 y hypotonia, left Babinski's sign, birth weight 1800 g. Nystagmus horizontal nystagmus first noted at 11 mth NE = not examined","unstructured":"Born at 30 weeks' gestation, At 1 y hypotonia, left Babinski's sign, birth weight 1800 g. Nystagmus horizontal nystagmus first noted at 11 mth NE = not examined."},{"key":"ref_2","first-page":"383","article-title":"The hereditary ataxias and paraplegias","volume-title":"Principles and practice of medical genetics","author":"Harding, A.E.","year":"1990","unstructured":"Harding AE. The hereditary ataxias and paraplegias. In: Emery AEH, Rimoin DL, eds. Principles and practice of medical genetics. Edinburgh: Churchill Livingstone, 1990:383-96."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1136\/jmg.13.3.217","article-title":"X-linked recessive type of pure spastic paraplegia in a large pedigree: absence of detectable linkage with Xg","volume":"13","author":"Zatz, M.; Penha-Serrano, C.; Otto, P.A.","year":"1976","unstructured":"Zatz M, Penha-Serrano C, Otto PA. X-linked recessive type of pure spastic paraplegia in a large pedigree: absence of detectable linkage with Xg. J Med Genet 1976;13:217-22.","journal-title":"J Med Genet"},{"key":"ref_4","first-page":"933","volume":"41","author":"Keppen, L.D.; Leppert, M.F.; O'Connell, P.O.","year":"1987","unstructured":"Keppen LD, Leppert MF, O'Connell PO, et al. Etiological heterogeneity in X-linked Genet 1987;41:933-43.","journal-title":"Etiological heterogeneity in X-linked Genet"},{"key":"ref_5","first-page":"13","article-title":"Hereditary cerebral palsy: a Johnston ApWre, liMmcinKaursyircekporVtA...7APesdeixa-tlrin1k9e5d7; r5e0ce:s4s5i4v-e8.form of spastic paraplegia","volume":"71","author":"Blumel, J.; Evans, E.B.; Eggers, G.W.N.","year":"1966","unstructured":"Blumel J, Evans EB, Eggers GWN. Hereditary cerebral palsy: a Johnston ApWre,liMmcinKaursyircekporVtA...7APesdeixa-tlrin1k9e5d7;r5e0ce:s4s5i4v-e8.form of spastic paraplegia. Am 7 Hum Baar HS, Gabriel AM. Sex-linked Ment Defic 1966;71:13-18.","journal-title":"Am 7 Hum Baar HS, Gabriel AM. Sex-linked Ment Defic"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1136\/jnnp.46.7.671","article-title":"Familial spastic paraplegia with Kallmann's syndrome","volume":"46","author":"Tuck, R.R.; O'Neil, B.P.; Gharib, H.; Mulder, D.W.","year":"1983","unstructured":"Tuck RR, O'Neil BP, Gharib H, Mulder DW. Familial spastic paraplegia with Kallmann's syndrome. Neurosurg Psychiatry 1983;46:671-4.","journal-title":"Neurosurg Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1007\/BF00401241","article-title":"Linkage studies of X-linked recessive spastic paraplegia DNA probes","volume":"73","author":"Kenwrick, S.; Ionasescu, V.; Ionasescu, G.","year":"1986","unstructured":"Kenwrick S, Ionasescu V, Ionasescu G, et al. Linkage studies of X-linked recessive spastic paraplegia DNA probes. Hum Genet 1986;73:264-6. using","journal-title":"Hum Genet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/j.1399-0004.1989.tb02915.x","article-title":"X-linked spastic paraplegia: evidence for homogeneity with a variable phenotype","volume":"35","author":"Goldblatt, J.; Ballo, R.; Sachs, B.; Moosa, A.","year":"1989","unstructured":"Goldblatt J, Ballo R, Sachs B, Moosa A. X-linked spastic paraplegia: evidence for homogeneity with a variable phenotype. Clin Genet 1989;35:116-20.","journal-title":"Clin Genet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/ajmg.1320340203","article-title":"Heterogeneity of X-linked recessive (spino)cerebellar ataxia with or without spastic diplegia","volume":"34","author":"Apak, S.; Yuksel, M.; Ozmen, M.; Saka, N.; Darendeliler, F.; Neuhauser, G.","year":"1989","unstructured":"Apak S, Yuksel M, Ozmen M, Saka N, Darendeliler F, Neuhauser G. Heterogeneity of X-linked recessive (spino)cerebellar ataxia with or without spastic diplegia. Am J Med Genet 1989;34:155-8.","journal-title":"Am J Med Genet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/0003-2697(84)90381-6","article-title":"A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity","volume":"137","author":"Feinberg, A.P.; Vogelstein, B.A.","year":"1984","unstructured":"Feinberg AP, Vogelstein BA. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 1984;137:266-7.","journal-title":"Anal Biochem"},{"key":"ref_11","first-page":"460","article-title":"Easy calculation of lod-scores and genetic risks","volume":"36","author":"Lathrop, G.M.; Lalouel, J.M.","year":"1984","unstructured":"Lathrop GM, Lalouel JM. Easy calculation of lod-scores and genetic risks 1984;36:460-5."},{"key":"ref_12","first-page":"3443","article-title":"Strategies for multilocus linkage","volume-title":"analysis in humans. Proc Natl Acad Sci USA","volume":"81","author":"Lathrop, G.M.; Lalouel, J.M.; Julier, C.; Ott, J.","year":"1984","unstructured":"Lathrop GM, Lalouel JM, Julier C, Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci USA 1984;81:3443-6."},{"key":"ref_13","first-page":"394","article-title":"Human Gene Mapping 10.5. Oxford Conference","volume":"55","year":"1990","unstructured":"Human Gene Mapping 10.5. Oxford Conference. Cytogenet Cell Genet 1990;55:394.","journal-title":"Cytogenet Cell Genet"},{"key":"ref_14","first-page":"429","article-title":"X linked complicated spastic paraplegia, MASA syndrome, and X linked hydrocephalus owing to congenital stenosis of the aqueduct of Sylvius: variable expression of the same mutation","volume":"28","author":"Fryns, J.P.; Spaepen, A.; Cassiman, J.J.; Van Den Berghe, H.","year":"1991","unstructured":"Fryns JP, Spaepen A, Cassiman JJ, Van Den Berghe H. X linked complicated spastic paraplegia, MASA syndrome, and X linked hydrocephalus owing to congenital stenosis of the aqueduct of Sylvius: variable expression of the same mutation at Xq28. _7 Med Genet 1991;28:429-31."},{"key":"ref_15","first-page":"515","article-title":"X-linked hydrocephalus: clinical heterogeneity Pediatr","volume":"151","author":"Serville, F.; Lyonnet, S.; Pelet, A.","year":"1992","unstructured":"Serville F, Lyonnet S, Pelet A, et al. X-linked hydrocephalus: clinical heterogeneity Pediatr 1992;151:515-18."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/j.1399-0004.1974.tb01697.x","article-title":"The MASA syndrome: a new heritable mental retardation syndrome","volume":"5","author":"Bianchine, J.W.; Lewis, R.C.","year":"1974","unstructured":"Bianchine JW, Lewis RC. The MASA syndrome: a new heritable mental retardation syndrome. Clin Genet 1974;5:298-306.","journal-title":"Clin Genet"},{"issue":"82","key":"ref_17","first-page":"367","article-title":"MASA syndrome: further clinical delineation and chromosomal location","volume":"1989","author":"Winter, R.M.; Davies, K.E.; Bell, M.V.; Huson, S.M.; Patterson, M.N.","unstructured":"Winter RM, Davies KE, Bell MV, Huson SM, Patterson MN. MASA syndrome: further clinical delineation and chromosomal location. Hum Genet 1989,82:367-70.","journal-title":"Hum Genet"},{"key":"ref_18","first-page":"887","article-title":"Invited editorial. Phenotypic heterogeneity and the single gene. Am.7 Hum Genet","volume":"50","author":"Suthers, G.K.; Davies, K.E.","year":"1992","unstructured":"Suthers GK, Davies KE. Invited editorial. Phenotypic heterogeneity and the single gene. 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