No evidence of locus heterogeneity in familial microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome

dc.contributor.authorSchlogel, Matthieuen_ZA
dc.contributor.authorMendola, Antonellaen_ZA
dc.contributor.authorFastre, Elodieen_ZA
dc.contributor.authorVasudevan, Pradeepen_ZA
dc.contributor.authorDevriendt, Koenen_ZA
dc.contributor.authorde Ravel, Thomyen_ZA
dc.contributor.authorVan Esch, Hildeen_ZA
dc.contributor.authorCasteels, Ingeleen_ZA
dc.contributor.authorArroyo Carrera, Ignacioen_ZA
dc.contributor.authorCristofoli, Francescaen_ZA
dc.contributor.authorFieggen, Karenen_ZA
dc.contributor.authorJones, Katherynen_ZA
dc.contributor.authorLipson, Marken_ZA
dc.contributor.authorBalikova,en_ZA
dc.date.accessioned2015-10-12T10:58:27Z
dc.date.available2015-10-12T10:58:27Z
dc.date.issued2015en_ZA
dc.description.abstractBACKGROUND:Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome (MCLMR) is a rare autosomal dominant disorder with variable expressivity. It is characterized by mild-to-severe microcephaly, often associated with intellectual disability, ocular defects and lymphedema. It can be sporadic or inherited. Eighty-seven patients have been described to carry a mutation in KIF11, which encodes a homotetrameric motor kinesin, EG5. METHODS: We tested 23 unreported MCLMR index patients for KIF11. We also reviewed the clinical phenotypes of all our patients as well as of those described in previously published studies. RESULTS: We identified 14 mutations, 12 of which are novel. We detected mutations in 12 affected individuals, from 6 out of 6 familial cases, and in 8 out of 17 sporadic patients. Phenotypic evaluation of patients (our 26+61 earlier published=87) revealed microcephaly in 91%, eye anomalies in 72%, intellectual disability in 67% and lymphedema in 47% of the patients. Unaffected carriers were rare (4 out of 87: 5%). Family history is not a requisite for diagnosis; 31% (16 out of 52) were de novo cases. CONCLUSIONS: All inherited cases, and 50% of sporadic cases of MCLMR are due to germline KIF11 mutations. It is possible that mosaic KIF11 mutations cause the remainder of sporadic cases, which the methods employed here were not designed to detect. On the other hand, some of them might have another mimicking disorder and genetic defect, as microcephaly is highly heterogeneous. In aggregate, KIF11 mutations likely cause the majority, if not all, of MCLMR.en_ZA
dc.identifier.apacitationSchlogel, M., Mendola, A., Fastre, E., Vasudevan, P., Devriendt, K., de Ravel, T., ... (2015). No evidence of locus heterogeneity in familial microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome. <i>Orphanet Journal of Rare Diseases</i>, http://hdl.handle.net/11427/14197en_ZA
dc.identifier.chicagocitationSchlogel, Matthieu, Antonella Mendola, Elodie Fastre, Pradeep Vasudevan, Koen Devriendt, Thomy de Ravel, Hilde Van Esch, et al "No evidence of locus heterogeneity in familial microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome." <i>Orphanet Journal of Rare Diseases</i> (2015) http://hdl.handle.net/11427/14197en_ZA
dc.identifier.citationSchlögel, M. J., Mendola, A., Fastré, E., Vasudevan, P., Devriendt, K., de Ravel, T. J., ... & Vikkula, M. (2015). No evidence of locus heterogeneity in familial microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome. Orphanet journal of rare diseases, 10(1), 52.en_ZA
dc.identifier.ris TY - Journal Article AU - Schlogel, Matthieu AU - Mendola, Antonella AU - Fastre, Elodie AU - Vasudevan, Pradeep AU - Devriendt, Koen AU - de Ravel, Thomy AU - Van Esch, Hilde AU - Casteels, Ingele AU - Arroyo Carrera, Ignacio AU - Cristofoli, Francesca AU - Fieggen, Karen AU - Jones, Katheryn AU - Lipson, Mark AU - Balikova, AB - BACKGROUND:Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome (MCLMR) is a rare autosomal dominant disorder with variable expressivity. It is characterized by mild-to-severe microcephaly, often associated with intellectual disability, ocular defects and lymphedema. It can be sporadic or inherited. Eighty-seven patients have been described to carry a mutation in KIF11, which encodes a homotetrameric motor kinesin, EG5. METHODS: We tested 23 unreported MCLMR index patients for KIF11. We also reviewed the clinical phenotypes of all our patients as well as of those described in previously published studies. RESULTS: We identified 14 mutations, 12 of which are novel. We detected mutations in 12 affected individuals, from 6 out of 6 familial cases, and in 8 out of 17 sporadic patients. Phenotypic evaluation of patients (our 26+61 earlier published=87) revealed microcephaly in 91%, eye anomalies in 72%, intellectual disability in 67% and lymphedema in 47% of the patients. Unaffected carriers were rare (4 out of 87: 5%). Family history is not a requisite for diagnosis; 31% (16 out of 52) were de novo cases. CONCLUSIONS: All inherited cases, and 50% of sporadic cases of MCLMR are due to germline KIF11 mutations. It is possible that mosaic KIF11 mutations cause the remainder of sporadic cases, which the methods employed here were not designed to detect. On the other hand, some of them might have another mimicking disorder and genetic defect, as microcephaly is highly heterogeneous. In aggregate, KIF11 mutations likely cause the majority, if not all, of MCLMR. DA - 2015 DB - OpenUCT DO - 10.1186/s13023-015-0271-4 DP - University of Cape Town J1 - Orphanet Journal of Rare Diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - No evidence of locus heterogeneity in familial microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome TI - No evidence of locus heterogeneity in familial microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome UR - http://hdl.handle.net/11427/14197 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14197
dc.identifier.urihttp://dx.doi.org/10.1186/s13023-015-0271-4
dc.identifier.vancouvercitationSchlogel M, Mendola A, Fastre E, Vasudevan P, Devriendt K, de Ravel T, et al. No evidence of locus heterogeneity in familial microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome. Orphanet Journal of Rare Diseases. 2015; http://hdl.handle.net/11427/14197.en_ZA
dc.language.isoengen_ZA
dc.publisherBiomed Centralen_ZA
dc.publisher.departmentDivision of Human Geneticsen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourceOrphanet Journal of Rare Diseasesen_ZA
dc.source.uriDMMR; EG5; FEVR; Gene; Intellectual disability; KIF11; MCLMR; MLCRD; Mutationen_ZA
dc.subject.otherDMMRen_ZA
dc.subject.otherEG5en_ZA
dc.subject.otherFEVRen_ZA
dc.subject.otherGeneen_ZA
dc.subject.otherIntellectual disabilityen_ZA
dc.subject.otherKIF11en_ZA
dc.subject.otherMCLMRen_ZA
dc.subject.otherMLCRDen_ZA
dc.subject.otherMutationen_ZA
dc.titleNo evidence of locus heterogeneity in familial microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndromeen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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