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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Meier-Gorlin syndrome genotype-phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis
European Journal of Human Genetics, Volume 20, No. 6, Year 2012
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Description
Meier-Gorlin syndrome (MGS) is an autosomal recessive disorder characterized by microtia, patellar aplasia/hypoplasia, and short stature. Recently, mutations in five genes from the pre-replication complex (ORC1, ORC4, ORC6, CDT1, and CDC6), crucial in cell-cycle progression and growth, were identified in individuals with MGS. Here, we report on genotype-phenotype studies in 45 individuals with MGS (27 females, 18 males; age 3 months-47 years). Thirty-five individuals had biallelic mutations in one of the five causative pre-replication genes. No homozygous or compound heterozygous null mutations were detected. In 10 individuals, no definitive molecular diagnosis was made. The triad of microtia, absent/hypoplastic patellae, and short stature was observed in 82% of individuals with MGS. Additional frequent clinical features were mammary hypoplasia (100%) and abnormal genitalia (42%; predominantly cryptorchidism and hypoplastic labia minora/majora). One individual with ORC1 mutations only had short stature, emphasizing the highly variable clinical spectrum of MGS. Individuals with ORC1 mutations had significantly shorter stature and smaller head circumferences than individuals from other gene categories. Furthermore, compared with homozygous missense mutations, compound heterozygous mutations appeared to have a more severe effect on phenotype, causing more severe growth retardation in ORC4 and more frequently pulmonary emphysema in CDT1. A lethal phenotype was seen in four individuals with compound heterozygous ORC1 and CDT1 mutations. No other clear genotype-phenotype association was observed. Growth hormone and estrogen treatment may be of some benefit, respectively, to growth retardation and breast hypoplasia, though further studies in this patient group are needed. © 2012 Macmillan Publishers Limited All rights reserved.
Authors & Co-Authors
de Munnik, Sonja A.
Netherlands, Nijmegen
Radboud University Medical Center
Bicknell, Louise S.
United Kingdom, Edinburgh
Western General Hospital
Aftimos, Salim
New Zealand, Auckland
Auckland City Hospital
Al-Aama, Jumana Yousuf
Saudi Arabia, Jeddah
King Abdulaziz University
van Bever, Yolande
Netherlands, Rotterdam
Erasmus Mc
Bober, Michael B.
United States, Wilmington
Alfred I. Dupont Hospital for Children
Clayton-Smith, Jill
United Kingdom, Manchester
The University of Manchester
Edrees, A.
Saudi Arabia, Jeddah
King Abdulaziz University
Feingold, Murray
United States, Waltham
National Birth Defects Center
Fryer, Alan E.
United Kingdom, Liverpool
Alder Hey Children's Hospital
van Hagen, Johanna M.
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Hennekam, Raoul C.M.
Netherlands, Amsterdam
Universiteit Van Amsterdam
Jansweijer, Maaike C.E.
Netherlands, Amsterdam
Emma Kinderziekenhuis
Johnson, Diana S.
United Kingdom, Sheffield
Sheffield Children's Hospital
Kant, Sarina G.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Opitz, John M.
United States, Salt Lake City
The University of Utah
Ramadevi, A. Radha
India, Hyderabad
Rainbow Children's Hospital
Reardon, William
Ireland, Dublin
Our Lady's Hospital for Sick Children
Ross, Alison
Unknown Affiliation
Sarda, Pierre
France, Montpellier
Hopital Arnaud de Villeneuve
Schrander-Stumpel, Constance T.R.M.
Netherlands, Maastricht
Universiteit Maastricht
Schoots, Jeroen
Netherlands, Nijmegen
Radboud University Medical Center
Temple, I. Karen
United Kingdom, Southampton
University of Southampton, Faculty of Medicine
Terhal, Paulien Anna
Netherlands, Utrecht
University Medical Center Utrecht
Toutain, Annick M.
France, Tours
Hopital Bretonneau
Wise, Carol A.
United States, Dallas
Texas Scottish Rite Hospital for Children
Wright, Michael J.
United Kingdom, Newcastle
Northern Genetics Service
Skidmore, David L.
Canada, Halifax
Iwk Health Centre
Canada, Halifax
Dalhousie University
Samuels, Mark E.
Canada, Montreal
Centre Hospitalier de L'universite de Montreal
Hoefsloot, Lies H.
Netherlands, Nijmegen
Radboud University Medical Center
Knoers, Nine V.A.M.
Netherlands, Utrecht
University Medical Center Utrecht
Brunner, Han G.
Netherlands, Nijmegen
Radboud University Medical Center
Jackson, Andrew P.
United Kingdom, Edinburgh
Western General Hospital
Bongers, Ernie M.H.F.
Netherlands, Nijmegen
Radboud University Medical Center
Statistics
Citations: 102
Authors: 34
Affiliations: 27
Identifiers
Doi:
10.1038/ejhg.2011.269
ISSN:
10184813
e-ISSN:
14765438
Research Areas
Genetics And Genomics
Health System And Policy
Participants Gender
Female