Evaluation of Clinical Manifestations in Patients with Severe Lymphedema with and without CCBE1 Mutations

被引:35
作者
Alders, M. [1 ]
Mendola, A. [2 ]
Ades, L. [3 ]
Al Gazali, L. [4 ]
Bellini, C. [5 ]
Dallapiccola, B. [6 ]
Edery, P. [7 ,8 ]
Frank, U. [9 ]
Hornshuh, F. [10 ]
Huisman, S. A. [11 ]
Jagadeesh, S. [12 ]
Kayserili, H. [13 ]
Keng, W. T. [14 ]
Lev, D. [15 ]
Prada, C. E. [16 ]
Sampson, J. R. [17 ]
Schmidtke, J. [18 ]
Shashi, V. [19 ]
van Bever, Y. [20 ]
Van der Aa, N. [21 ,22 ]
Verhagen, J. M. [20 ]
Verheij, J. B. [23 ]
Vikkula, M. [2 ,25 ]
Hennekam, R. C. [24 ]
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands
[2] Catholic Univ Louvain, de Duve Inst, Lab Human Mol Genet, Brussels, Belgium
[3] Univ Sydney, Paediat & Child Hlth, Sydney, NSW, Australia
[4] United Arab Emirates Univ, Dept Paediat, Al Ain, U Arab Emirates
[5] Univ Genoa, Gaslini Inst, Dept Paediat, Neonatal Intens Care Unit, Genoa, Italy
[6] IRCCS, Osped Pediat Bambino Gesu, Rome, Italy
[7] Hosp Civils Lyon, Serv Cytogenet Constitut, Bron, France
[8] Univ Lyon 1, INSERM, U1028, CNRS,UMR5292,CRNL,TIGER, Lyon, France
[9] Sozialpadiatr Zentrum, Braunschweig, Germany
[10] Univ Witten Herdecke, Vest Childrens Hosp Datteln, Dept Neonatol & Pediat Intens Care, Witten, Germany
[11] Ctr People Intellectual Disabil, Prinsenstichting, Purmerend, Netherlands
[12] Foetal Care Res, Genet Counselling Dept, Madras, Tamil Nadu, India
[13] Istanbul Univ, Istanbul Fac Med, Dept Med Genet, Istanbul, Turkey
[14] Kuala Lumpur Hosp, Dept Genet, Kuala Lumpur, Malaysia
[15] Inst Med Genet, Wolfson Med Ctr, Holon, Israel
[16] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA
[17] Inst Med Genet, Cardiff, S Glam, Wales
[18] Hannover Med Sch, Inst Humangenet, Hannover, Germany
[19] Duke Univ, Div Med Genet, Durham, NC USA
[20] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands
[21] Univ Hosp, Dept Med Genet, Antwerp, Belgium
[22] Univ Antwerp, Antwerp, Belgium
[23] Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands
[24] Univ Amsterdam, Acad Med Ctr, Dept Paediat, Amsterdam, Netherlands
[25] Catholic Univ Louvain, de Duve Inst, WELBIO Walloon Excellence Lifesci & Biotech, Brussels, Belgium
关键词
Autosomal recessive; CCBE1; Genotype-phenotype; Hennekam syndrome; Lymphangiectasia; Lymphatic dysplasia; Lymphedema;
D O I
10.1159/000342486
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The lymphedema-lymphangiectasia-intellectual disability (Hennekam) syndrome (HS) is characterised by a widespread congenital lymph vessel dysplasia manifesting as congenital lymphedema of the limbs and intestinal lymphangiectasia, accompanied by unusual facial morphology, variable intellectual disabilities and infrequently malformations. The syndrome is heterogeneous as mutations in the gene CCBE1 have been found responsible for the syndrome in only a subset of patients. We investigated whether it would be possible to predict the presence of a CCBE1 mutation based on phenotype by collecting clinical data of patients diagnosed with HS, with or without a CCBE1 mutation. We report here the results of 13 CCBE1 positive patients, 16 CCBE1 negative patients, who were clinically found to have classical HS, and 8 patients in whom the diagnosis was considered possible, but not certain, and in whom no CCBE1 mutation was identified. We found no statistically significant phenotypic differences between the 2 groups with the clinical HS phenotype, although the degree of lymphatic dysplasia tended to be more pronounced in the mutation positive group. We also screened 158 patients with less widespread and less pronounced forms of lymphatic dysplasia for CCBE1 mutations, and no mutation was detected in this group. Our results suggest that (1) CCBE1 mutations are present only in patients with a likely clinical diagnosis of HS, and not in patients with less marked forms of lymphatic dysplasia, and (2) that there are no major phenotypic differences between HS patients with or without CCBE1 mutations. Copyright (C) 2012 S. Karger AG, Basel.
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收藏
页码:107 / 113
页数:7
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