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

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Schlögel, Matthieu [UCL] Mendola, Antonella [UCL] Fastre, Elodie [UCL] Vasudevan, Pradeep [University Hospitals of Leicester] Devriendt, Koen [University Hospitals Leuven] Revencu, Nicole [UCL] Boon, Laurence M. [UCL] Brouillard, Pascal [UCL] Vikkula, Miikka [UCL]

(eng) 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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2015
Language Anglais
Journal information "Orphanet Journal of Rare Diseases" - Vol. 10, no. 1, p. 52 (2015)
Peer reviewed yes
Publisher BioMed Central Ltd. ((United Kingdom) London)
e-issn 1750-1172
Publication status Publié
Affiliations UCL - (SLuc) Centre de génétique médicale UCL
UCL - (SLuc) Service de chirurgie plastique
UCL - SSS/DDUV/GEHU - Génétique
Keywords CDMMR ; EG5 ; FEVR ; Gene ; Intellectual disability ; KIF11 ; MCLMR ; MLCRD ; Mutation
Links
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Bibliographic reference Schlögel, Matthieu ; Mendola, Antonella ; Fastre, Elodie ; Vasudevan, Pradeep ; Devriendt, Koen ; et. al. No evidence of locus heterogeneity in familial microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome.. In: Orphanet Journal of Rare Diseases, Vol. 10, no. 1, p. 52 (2015)
Permanent URL http://hdl.handle.net/2078.1/160923