No evidence of locus heterogeneity in familial microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome
dc.contributor.author | Schlogel, Matthieu | en_ZA |
dc.contributor.author | Mendola, Antonella | en_ZA |
dc.contributor.author | Fastre, Elodie | en_ZA |
dc.contributor.author | Vasudevan, Pradeep | en_ZA |
dc.contributor.author | Devriendt, Koen | en_ZA |
dc.contributor.author | de Ravel, Thomy | en_ZA |
dc.contributor.author | Van Esch, Hilde | en_ZA |
dc.contributor.author | Casteels, Ingele | en_ZA |
dc.contributor.author | Arroyo Carrera, Ignacio | en_ZA |
dc.contributor.author | Cristofoli, Francesca | en_ZA |
dc.contributor.author | Fieggen, Karen | en_ZA |
dc.contributor.author | Jones, Katheryn | en_ZA |
dc.contributor.author | Lipson, Mark | en_ZA |
dc.contributor.author | Balikova, | en_ZA |
dc.date.accessioned | 2015-10-12T10:58:27Z | |
dc.date.available | 2015-10-12T10:58:27Z | |
dc.date.issued | 2015 | en_ZA |
dc.description.abstract | 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. | en_ZA |
dc.identifier.apacitation | Schlogel, 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/11427/14197 | en_ZA |
dc.identifier.chicagocitation | Schlogel, 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/11427/14197 | en_ZA |
dc.identifier.citation | Schlögel, 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.uri | http://hdl.handle.net/11427/14197 | |
dc.identifier.uri | http://dx.doi.org/10.1186/s13023-015-0271-4 | |
dc.identifier.vancouvercitation | Schlogel 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.iso | eng | en_ZA |
dc.publisher | Biomed Central | en_ZA |
dc.publisher.department | Division of Human Genetics | en_ZA |
dc.publisher.faculty | Faculty of Health Sciences | en_ZA |
dc.publisher.institution | University of Cape Town | |
dc.rights | This is an Open Access article distributed under the terms of the Creative Commons Attribution License | en_ZA |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0 | en_ZA |
dc.source | Orphanet Journal of Rare Diseases | en_ZA |
dc.source.uri | DMMR; EG5; FEVR; Gene; Intellectual disability; KIF11; MCLMR; MLCRD; Mutation | en_ZA |
dc.subject.other | DMMR | en_ZA |
dc.subject.other | EG5 | en_ZA |
dc.subject.other | FEVR | en_ZA |
dc.subject.other | Gene | en_ZA |
dc.subject.other | Intellectual disability | en_ZA |
dc.subject.other | KIF11 | en_ZA |
dc.subject.other | MCLMR | en_ZA |
dc.subject.other | MLCRD | en_ZA |
dc.subject.other | Mutation | en_ZA |
dc.title | No evidence of locus heterogeneity in familial microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome | en_ZA |
dc.type | Journal Article | en_ZA |
uct.type.filetype | Text | |
uct.type.filetype | Image | |
uct.type.publication | Research | en_ZA |
uct.type.resource | Article | en_ZA |
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