Molecular genetic analysis of the multiple pterygium syndromes

Abstract for presentation at 11th International Congress of Human Genetics

Neil Morgan, Section of Medical and Molecular Genetics, Division of Reproductive and Child Health, University of Birmingham, Birmingham, United Kingdom

Louise Brueton, Clinical Genetics Unit, Birmingham Women’s Hospital, Birmingham, United Kingdom

Phillip Cox, Department of Pathology, Birmingham Women’s Hospital, Birmingham, United Kingdom

Marie Greally, Saad Specialist Hospital, Kingdom of Saudi Arabia, Saudi Arabia

John Tolmie, Department of Clinical Genetics, Royal Hospital for Sick Children, Glasgow, United Kingdom

Shanaz Pasha, Section of Medical and Molecular Genetics, Division of Reproductive and Child Health, University of Birmingham, Birmingham, United Kingdom

Dr Christine Oley, Clinical Genetics Unit, Birmingham Women's Hospital, United Kingdom

Dr Julie Vogt, Clinical Genetics Unit, Birmingham Women's Hospital, Birmingham, United Kingdom

Han Brunner, Department of Human Genetics 417, University Medical Centre Nijmegen, The Netherlands

Eamonn Maher, Section of Medical and Molecular Genetics, Division of Reproductive and Child Health, University of Birmingham, Birmingham, United Kingdom

Multiple pterygium syndromes (MPS) comprise a group of multiple congenital anomaly disorders characterised by webbing (pterygia) of the neck, elbows and/or knees and joint contractures (athrogryposis). MPS are phenotypically and genetically heterogeneous, but are traditionally divided into prenatally lethal and non-lethal (Escobar) types.
To elucidate the pathogenesis of MPS, we undertook a genome-wide linkage scan in a large consanguineous family and mapped a novel MPS locus. We then identified germline inactivating mutations in an acetylcholine receptor subunit in families with MPS. Genotype-phenotype correlations will be presented.
These findings extend the role of acetylcholine receptor dysfunction in human disease and provide new insights into the pathogenesis and management of fetal akinesia syndromes.