{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:55:31Z","timestamp":1791665731090,"version":"4.3.4"},"reference-count":27,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1997,3]]},"abstract":"<jats:p>X linked subcortical laminar heterotopia and lissencephaly syndrome (XSCLH\/ LIS) is an intriguing disorder of cortical development, which causes classical lissencephaly with severe mental retardation and epilepsy in hemizygous males, and subcortical laminar heterotopia (SCLH) associated with milder mental retardation and epilepsy in heterozygous females. Here we report an exclusion mapping study carried out in three unrelated previously described families in which males are affected with lissencephaly and females with SCLH, using 38 microsatellite markers evenly distributed on the X chromosome. Most of the X chromosome was excluded and potential intervals of assignment in Xq22.3-q23 or in Xq27 are reported. Although the number of informative meioses did not allow a decision between these two loci, it is worth noting that the former interval is compatible with the mapping of a breakpoint involved in a de novo X;autosomal balanced translocation 46,XX,t(X;2)(q22;p25) previously described in a female with classical lissencephaly. In addition, haplotype inheritance in two families showed a grandpaternal origin of the mutation and suggested in one family the presence of mosaicism in germline cells of normal transmitting males.<\/jats:p>","DOI":"10.1136\/jmg.34.3.177","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"177-183","source":"Crossref","is-referenced-by-count":49,"title":["Dominant X linked subcortical laminar heterotopia and lissencephaly syndrome (XSCLH\/LIS): evidence for the occurrence of mutation in males and mapping of a potential locus in Xq22."],"prefix":"10.1136","volume":"34","author":[{"given":"V","family":"des Portes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J M","family":"Pinard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Smadja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Motte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Boespfl\u00fcg-Tanguy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M L","family":"Moutard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Desguerre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Billuart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Carrie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Bienvenu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M C","family":"Vinet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Bachner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Beldjord","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Dulac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Kahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Ponsot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Chelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1997,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1093\/brain\/118.3.629","article-title":"Abnormalities of gyration, heterotopias, tuberous sclerosis, focal cortical dysplasia, microdysgenesis, dysembryoplastic neuroepithelial tumor and dysgenesis of the archicortex in epilepsy. Clinical, EEG and neuroimaging features in 100 adults patients","volume":"118","author":"Raymond, A.; Fish, D.; Sisodiya, S.; Alsanjari, N.; Stevens, J.; Shorvon, S.","year":"1995","unstructured":"Raymond A, Fish D, Sisodiya S, Alsanjari N, Stevens J, Shorvon S. Abnormalities of gyration, heterotopias, tuberous sclerosis, focal cortical dysplasia, microdysgenesis, dysembryoplastic neuroepithelial tumor and dysgenesis of the archicortex in epilepsy. Clinical, EEG and neuroimaging features in 100 adults patients. Brain 1995;118:629-60.","journal-title":"Brain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1212\/WNL.41.10.1656","article-title":"Diffuse cortical dysplasia, or the \"double cortex\" syndrome: the clinical and epileptic spectrum in 10 patients","volume":"41","author":"Palmini, A.; Andermann, F.; Aicardi, J.","year":"1991","unstructured":"Palmini A, Andermann F, Aicardi J, et al. Diffuse cortical dysplasia, or the \"double cortex\" syndrome: the clinical and epileptic spectrum in 10 patients. Neurology 1991;41: 1656-62.","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/ana.410360409","article-title":"Band heterotopia: correlation of outcome with magnetic resonance imaging parameters","volume":"36","author":"Barkovich, A.; Guerrini, R.; Battaglia, G.","year":"1994","unstructured":"Barkovich A, Guerrini R, Battaglia G, et al. Band heterotopia: correlation of outcome with magnetic resonance imaging parameters. Ann Neurol 1994;36:609-17.","journal-title":"Ann Neurol"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1136\/jnnp.57.8.914","article-title":"Subcortical laminar heterotopia and lissencephaly in two families: a single X linked dominant gene","volume":"57","year":"1994","unstructured":"Pinard JM, Motte J, Chiron C, Brian R, Andermann E, Dulac 0. Subcortical laminar heterotopia and lissencephaly in two families: a single X linked dominant gene. J Neurol Neurosurg Psychiatry 1994;57:914-20.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1055\/s-2007-979717","article-title":"Band brain heterotopia. Case report and literature review","volume":"26","author":"Franzoni, E.; Bernardi, B.; Marchiarni, V.; Crisanti, A.; Marchi, R.; Fonda, C.","year":"1995","unstructured":"Franzoni E, Bernardi B, Marchiarni V, Crisanti A, Marchi R, Fonda C. Band brain heterotopia. Case report and literature review. Neuropediatrics 1995;26:37-40.","journal-title":"Neuropediatrics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0387-7604(12)80289-0","article-title":"The agyria-pachygyria complex: a spectrum of cortical malformations","volume":"13","author":"Aicardi, J.","year":"1991","unstructured":"Aicardi J. The agyria-pachygyria complex: a spectrum of cortical malformations. Brain Dev 1991;13:1-8.","journal-title":"Brain Dev"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1212\/WNL.42.7.1375","article-title":"Causal heterogeneity in isolated lissencephaly","volume":"42","author":"Dobyns, W.; Elias, E.; Newlin, A.; Pagon, R.; Ledbetter, D.","year":"1992","unstructured":"Dobyns W, Elias E, Newlin A, Pagon R, Ledbetter D. Causal heterogeneity in isolated lissencephaly. Neurology 1992;42: 1375-88. application of this model to XSCLH\/LIS syndrome would also integrate the notable","journal-title":"Neurology"},{"key":"ref_8","article-title":"Autosomal recessive eye and brain anomalies: Warburg syndrome","author":"Pagon, R.; Clarren, S.; Millam, D.; Hendrickson, A.","year":"1983","unstructured":"Pagon R, Clarren S, Millam D, Hendrickson A. Autosomal recessive eye and brain anomalies: Warburg syndrome. J Pediatr 1983;102:542-6. worsening of phenotype in females across generations in families 2 and 3. Although a skewed inactivation of the X chromosomes cannot be ruled out, this latter phenomenon can hardly explain this striking worsening of the daughters' phenotype with respect to their mother. It is interesting to point out that either one of the two hypotheses, male germline mosaicism or dynamic mutation, could reliably be used to explain the segration of the disease in the extended family 3, including the two atypical","journal-title":"J Pediatr; 102: 542-6. worsening of phenotype in females across generations in families 2 and 3. Although a skewed inactivation of the X chromosomes cannot be ruled out, this latter phenomenon can hardly explain this striking worsening of the daughters' phenotype with respect to their mother. It is interesting to point out that either one of the two hypotheses, male germline mosaicism or dynamic mutation, could reliably be used to explain the segration of the disease in the extended family 3, including the two atypical"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/364717a0","article-title":"Isolation of a Miller-Dieker lissencephaly gene containing G protein b-subunit-like repeats","volume":"364","author":"Reiner 0, Carrozzo R, Shen Y","year":"1993","unstructured":"Reiner 0, Carrozzo R, Shen Y, et al. Isolation of a Miller-Dieker lissencephaly gene containing G protein b-subunit-like repeats. Nature 1993;364:717-21.","journal-title":"Nature"},{"key":"ref_10","first-page":"182","article-title":"Microdeletions of chromosome 17p 13 as a cause of isolated lissencephaly","volume":"50","author":"Ledbetter, S.; Kuwano, A.; Dobyns, W.; Ledbetter, D.","year":"1992","unstructured":"Ledbetter S, Kuwano A, Dobyns W, Ledbetter D. Microdeletions of chromosome 17p 13 as a cause of isolated lissencephaly. Am J Hum Genet 1992;50:182-9.","journal-title":"Am J Hum Genet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1212\/WNL.44.1.51","article-title":"Periventricular heterotopia and epilepsy","volume":"44","author":"Huttenlocher, P.; Taravath, S.; Mojtahedi, S.","year":"1994","unstructured":"Huttenlocher P, Taravath S, Mojtahedi S. Periventricular heterotopia and epilepsy. Neurology 1994;44:51-5.","journal-title":"Neurology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1212\/WNL.43.7.1424","article-title":"Familial band heterotopias simulating tuberous sclerosis","volume":"43","author":"DiMario, F.; Cobb, R.; Ramsby, G.; Leicher, C.","year":"1993","unstructured":"DiMario F, Cobb R, Ramsby G, Leicher C. Familial band heterotopias simulating tuberous sclerosis. Neurology 1993; 43:1424-6.","journal-title":"Neurology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0896-6273(00)80025-2","article-title":"Periventricular heterotopia: an X-linked dominant epilepsy locus causing aberrant cerebral cortical development","volume":"16","author":"Eksioglu, Y.; Scheffer, I.; Cardenas, P.","year":"1996","unstructured":"Eksioglu Y, Scheffer I, Cardenas P, et al. Periventricular heterotopia: an X-linked dominant epilepsy locus causing aberrant cerebral cortical development. Neuron 1996;16: 77-87.","journal-title":"Neuron"},{"key":"ref_14","article-title":"X-linked forms of SCLH observed in II.10 and III.8, and the inheritance of the abnormal chromosome in the healthy boy III.2 (fig IA). To evaluate the linkage between the disease and malformations of neuronal migration","author":"Dobyns, W.; Andermann, E.; Andermann, F.","unstructured":"Dobyns W, Andermann E, Andermann F, et al. X-linked forms of SCLH observed in II.10 and III.8, and the inheritance of the abnormal chromosome in the healthy boy III.2 (fig IA). To evaluate the linkage between the disease and malformations of neuronal migration. Neurology (in press)."},{"key":"ref_15","first-page":"171","article-title":"H&t&rotopies laminaires sous-corticales et lissencephalie: malformations cerebrales d'origine familiale commune, liee a l'X","volume":"151","year":"1995","unstructured":"Pinard JM, Desguerre I, Motte J, Dulac 0, Ponsot G. H&t&rotopies laminaires sous-corticales et lissencephalie: malformations cerebrales d'origine familiale commune, liee a l'X. Rev Neurol 1995;151:171-6.","journal-title":"Rev Neurol"},{"key":"ref_16","article-title":"Subcortical laminar heterotopia and other markers of the X chromosome, taking into account the extended family 3 together with X-linked cerebral cortical dysgenesis","volume-title":"Trends in child neurology","author":"Pinard, J.M.","year":"1996","unstructured":"Pinard JM. Subcortical laminar heterotopia and other markers of the X chromosome, taking into account the extended family 3 together with X-linked cerebral cortical dysgenesis. In: Arzimanoglou A, Goutieres F, eds. Trends in child neurology. Paris: John Libbey Eurotext, 1996."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/ng0694supp-246","article-title":"The 1993-94 Genethon human genetic linkage map","volume":"7","author":"Gyapay, G.; Morissette, J.; Vignal, A.","year":"1994","unstructured":"Gyapay G, Morissette J, Vignal A, et al. The 1993-94 Genethon human genetic linkage map. Nat Genet 1994;7:246-339.","journal-title":"Nat Genet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/380152a0","article-title":"A comprehensive genetic map of the human genome based on 5.264 microsatellites","volume":"380","author":"Dib, C.; Faure, S.; Fizames, C.","year":"1996","unstructured":"Dib C, Faure S, Fizames C, et al. A comprehensive genetic map of the human genome based on 5.264 microsatellites. Nature 1996;380:152-4.","journal-title":"Nature"},{"key":"ref_19","first-page":"482","article-title":"Easy calculations of lod scores and genetic risks on small computers?","volume":"37","author":"Lathrop, G.M.; Lalouel, J.M.","year":"1984","unstructured":"Lathrop GM, Lalouel JM. Easy calculations of lod scores and genetic risks on small computers? Am J Hum Genet 1984;37:482-98.","journal-title":"Am J Hum Genet"},{"key":"ref_20","first-page":"252","article-title":"Faster sequential genetic linkage computations","volume":"53","author":"Cottingham, R.W.; Idury, R.M.; Schaffer, A.","year":"1993","unstructured":"Cottingham RW, Idury RM, Schaffer A. Faster sequential genetic linkage computations. Am J Humn Genet 1993;53: 252-63.","journal-title":"Am J Humn Genet"},{"key":"ref_21","article-title":"Analysis of human genetic linkage. Revised edition","author":"Ott, J.","year":"1991","unstructured":"Ott J. Analysis of human genetic linkage. Revised edition. Baltimore: Johns Hopkins University Press, 1991."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1136\/jnnp.53.7.617","article-title":"Unusual MRI appearance of diffuse subcortical heterotopia or \"double cortex\"","volume":"53","author":"Livingston, J.; Aicardi, J.","year":"1990","unstructured":"Livingston J, Aicardi J. Unusual MRI appearance of diffuse subcortical heterotopia or \"double cortex\" in two children. -7 Neurol Neurosurg Psychiatry 1990;53:617-20.","journal-title":"in two children. -7 Neurol Neurosurg Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/ana.410360216","article-title":"X-linked pachygyria and agenesis of the corpus callosum: evidence for an X chromosome lissencephaly locus","volume":"36","author":"Berry-Kravis, E.; Israel, J.","year":"1994","unstructured":"Berry-Kravis E, Israel J. X-linked pachygyria and agenesis of the corpus callosum: evidence for an X chromosome lissencephaly locus. Ann Neurol 1994;36:229-33.","journal-title":"Ann Neurol"},{"key":"ref_24","first-page":"452","article-title":"New XLMR syndrome with characteristic face, hypogeni- Investigation of more families and further linkage studies should allow the genetic interval to be refined, and identification of the gene will elucidate underlying molecular and genetic talism, congenital hypotonia and pachygyria","volume":"43","author":"Zollino, M.; Mastroiacovo, P.; Zampino, G.; Mariotti, P.; Neri, G.","year":"1992","unstructured":"Zollino M, Mastroiacovo P, Zampino G, Mariotti P,Neri G. New XLMR syndrome with characteristic face, hypogeni- Investigation of more families and further linkage studies should allow the genetic interval to be refined, and identification of the gene will elucidate underlying molecular and genetic talism, congenital hypotonia and pachygyria. Am _7 Med Genet 1992;43:452-7.","journal-title":"Am _7 Med Genet"},{"key":"ref_25","first-page":"1364","article-title":"High male:female ratio of germ-line mutations: an alternative explanation for postulated gestational lethality in males in X-linked dominant disorders","volume":"58","author":"Thomas, G.","year":"1996","unstructured":"Thomas G. High male:female ratio of germ-line mutations: an alternative explanation for postulated gestational lethality in males in X-linked dominant disorders. Am ] Hum Genet 1996;58:1364-8.","journal-title":"Am"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/BF00291644","article-title":"Further segregation analysis of the fragile X syndrome with special reference to transmitting males","volume":"69","author":"Sherman, S.; Jacobs, P.; Morton, N.","year":"1985","unstructured":"Sherman S, Jacobs P, Morton N, et al. Further segregation analysis of the fragile X syndrome with special reference to transmitting males. Hum Genet 1985;69:289-99.","journal-title":"Hum Genet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1126\/science.252.5009.1097","article-title":"Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome","volume":"252","author":"Oberle, I.; Rousseau, F.; Heitz, D.","year":"1991","unstructured":"Oberle I, Rousseau F, Heitz D, et al. Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science 1991;252:1097-102.","journal-title":"Science"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.34.3.177","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T08:12:46Z","timestamp":1760775166000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.34.3.177"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,3]]},"references-count":27,"journal-issue":{"issue":"3","published-online":{"date-parts":[[1997,3,1]]},"published-print":{"date-parts":[[1997,3]]}},"alternative-id":["10.1136\/jmg.34.3.177"],"URL":"https:\/\/doi.org\/10.1136\/jmg.34.3.177","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,3]]}}}