MPI für molekulare Genetik / Department of Human Molecular Genetics |
|Mild phenotypes in a series of patients with Opitz GBBB syndrome with MID1 mutations|
|Authors:||So, Joyce; Suckow, Vanessa; Kijas, Zofia; Kalscheuer, Vera; Moser, Bettina; Winter, Jennifer; Baars, Marieke; Firth, Helen; Lunt, Peter; Hamel, Ben; Meinecke, Peter; Moraine, Claude; Odent, Sylvie; Schinzel, Albert; van der Smagt, J.J.; Devriendt, Koen; Albrecht, Beate; Gillessen-Kaesbach, Gabriele; van der Burgt, Ineke; Petrij, Fred; Faivre, Laurence; McGaughran, Julie; McKenzie, Fiona; Opitz, John M.; Cox, Timothy; Schweiger, Susann|
|Date of Publication (YYYY-MM-DD):||2006-11-19|
|Title of Journal:||American Journal of Medical Genetics Part A|
|Issue / Number:||1|
|Copyright:||Copyright © 2004 Wiley-Liss, Inc.|
|Review Status:||not specified|
|Abstract / Description:||Opitz syndrome (OS; MIM 145410 and MIM 300000) is a congenital midline malformation syndrome characterized by hypertelorism, hypospadias, cleft lip/palate, laryngotracheoesophageal (LTE) abnormalities, imperforate anus, developmental delay, and cardiac defects. The X-linked form (XLOS) is caused by mutations in the MID1 gene, which encodes a microtubule-associated RBCC protein. In this study, phenotypic manifestations of patients with and without MID1 mutations were compared to determine genotype-phenotype correlations. We detected 10 novel mutations, 5 in familial cases, 2 in sporadic cases, and 3 in families for whom it was not clear if they were familial or sporadic. The genotype and phenotype was compared for these 10 families, clinically diagnosed OS patients found not to have MID1 mutations, and 4 families in whom we have previously reported MID1 mutations. This combined data set includes clinical and mutation data on 70 patients. The XLOS patients with MID1 mutations were less severely affected than patients with MID1 mutations reported in previous studies, particularly in functionally significant neurologic, LTE, anal, and cardiac abnormalities. Minor anomalies were more prevalent in patients with MID1 mutations compared to those without mutations in this study. Female MID1 mutation carriers had milder phenotypes compared to male MID1 mutation carriers, with the most common manifestation being hypertelorism in both sexes. Most of the anomalies found in the patients of the present study do not correlate with the MID1 mutation type, with the possible exception of LTE malformations. This study demonstrates the wide spectrum of severity and manifestations of OS. It also shows that XLOS patients with MID1 mutations may be less severely affected than indicated in prior reports.
This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299/suppmat/index.html.
|Free Keywords:||X-linked Opitz syndrome • MID1 • phenotypic variability|
|Comment of the Author/Creator:||Funded by:
Deutsche Forschungsgemeinschaft; Grant Number: SFB 577
National Health and Medical Research Council of Australia; Grant Number: 157958, 997706.
Correspondence to Susann Schweiger, Ihnestrasse 73, 14195 Berlin, Germany.
|External Publication Status:||published|
|Communicated by:||Hans-Hilger Ropers|
|Affiliations:||MPI für molekulare Genetik|
|External Affiliations:||1.The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada;
2.Department of Clinical Genetics and Human Genetics, VU University Medical Center, Amsterdam, The Netherlands;
3.Department of Medical Genetics, Addenbrooke's Hospital, Cambridge, United Kingdom;
4.Clinical Genetics Service, St. Michael's Hospital, Bristol, United Kingdom;
5.Department of Human Genetics, University Medical Center, Nijmegen, The Netherlands;
6.Medizinische Genetik, Altonaer Kinderkrankenhaus, Hamburg, Germany;
7.Service de Genetique, Centre Hospitalier Universitaire de Tours, Hopital Bretonneau, Tours, France;
8.Genetique Medicale, Hopital Sud, Rennes, France;
9.Institute of Medical Genetics, University of Zurich, Zurich, Switzerland;
10.Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands;
11.Center for Human Genetics, Universitaire Ziekenhuizen Leuven, Leuven, Belgium;
12.Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany;
13.Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands;
14.Centre for Genetics, Hopital D'Enfants, Dijon, Cedex, France;
15.Queensland Clinical Genetics Service, Royal Children's Hospital and Health District, Herston, Queensland, Australia;
16.Hunter Genetics and University of Newcastle, Newcastle, New South Wales, Australia;
17.University of Utah School of Medicine, Salt Lake City, Utah, USA;
18.Department of Molecular Biosciences and ARC Special Research Centre for the Molecular Genetics of Development, Adelaide University, Adelaide, South Australia, Australia1.
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