Abstract
With a prevalence of approximately 1/10 000, and a carrier frequency of 1/40–1/60 the proximal spinal muscular atrophies (SMAs) are among the most frequent autosomal recessive hereditary disorders. Patients can be classified clinically into four groups: acute, intermediate, mild, and adult (SMA types I, II, III, and IV, respectively). The complexity and instability of the genomic region at chromosome 5q13 harbouring the disease-causing survival motor neuron 1 (SMN1) gene hamper molecular diagnosis in SMA. In addition, affected individuals with SMA-like phenotypes not caused by SMN1, and asymptomatic individuals with two mutant alleles exist. The SMN gene is present in at least one telomeric (SMN1) and one centromeric copy (SMN2) per chromosome in normal (non-carrier) individuals, although chromosomes containing more copies of SMN1 and/or SMN2 exist. Moreover, the two SMN genes (SMN1 and SMN2) are highly homologous and contain only five base-pair differences within their 3′ ends. Also, a relatively high de novo frequency is present in SMA. Guidelines for molecular analysis in diagnostic applications, carrier detection, and prenatal analysis using direct and indirect approaches are described. Overviews of materials used in the molecular diagnosis as well as Internet resources are included.
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Acknowledgements
We thank Prof Charles HCM Buys and Dr Robert MW Hofstra for critical reading and valuable contributions to the discussion paper prior to the meeting, and all participants of the best practice meeting for their suggestions and additions.
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These guidelines are the result of a best practice meeting funded by the European Molecular Genetics Quality Network (EMQN) in Groningen, The Netherlands on 21 September 2000. A list of participants is presented in Appendix 1.
Appendix 1
Appendix 1
Participants EMQN SMA Best Practice Meeting (2000) Groningen, The Netherlands
Vesa Juvonen, University of Turku, Department of Medical Genetics, Kiinamyllynkatu 10, FIN-20520 Turku, Finland
E-mail: vesa.juvonen@utu.fi
Rosario dos Santos, Instituto de Genética Médica Jacinto d, Praça Pedro Nunes 74, P-4000 Porto, Portugal
E-mail: rosario.santos@igm.min-saude.pt
Elaine Robertson, Kennedy Galton Centre, North West London Hospitals NHS Trust, Waterford Road, Harrow HA1 3UJ, United Kingdom
E-mail: s.j.payne@ic.ac.uk
Alessandra Tacconelli, Università degli Studi di Roma Tor Vergata, Dipartemento di Biopatologica e Diagnostica per Immagini, Edificio E Nord pt. Terra, Via di Tor Vergata 135, I-00133 ROMA, Italy
E-mail: Novelli@med.uniroma2.it
Maggie Williams, Southmead Hospital, Molecular Genetics Unit, Bristol, BS10 5NB, United Kingdom
E-mail: williamsmag@yahoo.com
Gert Matthijs, Katholieke Universiteit Leuven, Centre for Human Genetics, Gasthuisberg ON 6, Herestraat 49, B-3000 Leuven, Belgium
E-mail: Gert.Matthijs@med.kuleuven.ac.be
Francine Thonney, Genetique Medicale, CHUV, 1011 Lausanne, Switzerland
E-mail: Francine.thonney@hospvd.ch
Kyproula Christodoulou, The Cyprus Institute of Neurology and Genetics, 6 International Airport Ave, PO Box 23462, 1683 Nicosia, Cyprus
E-mail: Roula@mdrtc.cing.ac.cy
Hiljar Sibul, Tartu University, Molecular Diagnostics Centre, United Laboratories, Oru 3 St. 51005 Tartu, Estonia
E-mail: Hsibul@ebc.ee
Marianne Schwartz, Department of Clinical Genetics, Rigshopitalet 4062, Blegdamsvej 9, DK-2100, Copenhagen, Denmark
E-mail: Schwartz@rh.dk
Eva Bjorck, Sahlgrenska University Hospital, Department of Clinical Genetics, Pital-East, 416 85 Gothenburg, Sweden
E-mail: Eva.bjorck@obgyn.se
Veronika Karcagi, Dept of Biochemistry, National Institute of Environmental Health, Gyali u. 2-6, 1097 Budapest, Hungary
E-mail: Karcagi@oki1.joboki.hu
Vickey Lindley, Birmingham Women's Hospital, Regional Genetics Service, DNA Laboratory, Edgbaston, Birmingham, B15 2TH, United Kingdom
E-mail: fiona.macdonald@bham-womens.thenhs.com
Aileen Butler, National Center for Medical Genetics, Our Lady's Hospital for Sick Children, Crumlin, Dublin 12, Ireland
E-mail: aileen.butler@olhsc.ie
Gerhard Meng, Institut fur Humangenetik, Biozentrum, AmHubland, D97074 Wuerzburg, Germany
E-mail: gmeng@biozentrum.uni-wuerzburg.de
Sara Seneca, Vrije Universiteit Brussel, Dienst Medische Genetica VUB, Laarbeeklaan 101, B-1090 Bruxelles, Belgium
E-mail: lgensas@az.vub.ac.be
Willy Lissens, Vrije Universiteit Brussel, Dienst Medische Genetica VUB, Laarbeeklaan 101, B-1090 Bruxelles, Belgium
E-mail: lgenlsw@az.vub.ac.be
André Reeber, CNRS INSERM Université Louis Pasteur, Diagnostic Genetique, 11 Rue Humann, F-67085 Strasbourg Cedex, France
E-mail: areeb@igbmc.u-strasbg.fr
Mireille Cossee, CNRS INSERM Université Louis Pasteur, Diagnostic Genetique, 11 Rue Humann, F-67085 Strasbourg Cedex, France
E-mail: cossee@igbmc.u-strasbg.fr
Kiriaki Kekoy, Dept of Medical Genetics, Athens University, ‘Aghia Sophia’ Children's Hospital, Athens, Greece
E-mail: kkekou@cc.uoa.gr
Angela Apessos, Alfa lab, Medical Institute of Research and Diagnosis S.A., 8, Anastasiou str., 115 25 Athens, Greece
E-mail: angelaa@hol.gr
Jan Maarten Cobben, Academisch Ziekenhuis Vrije Universiteit, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
E-mail: JM.Cobben@azvu.nl
Marianne de Visser, Academisch Medisch Centrum, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
E-mail: M.deVisser@amc.uva.nl
Brunhilde Wirth, Institute of Human Genetics, Univ. of Bonn, Wilhelmstrasse 31, 53111 Bonn, Germany
E-mail: bwirth@uni-bonn.de
Su Stenhouse, Northern Regional Genetics Service, 19/20 Claremont Place, Newcastle upon Tyne NE2 4AA, United Kingdom
E-mail: s.a.r.stenhouse@ncl.ac.uk
Hans Scheffer, Dept. of Medical Genetics, Univ. of Groningen, Antonius Deusinglaan 4, 9713 AW Groningen, The Netherlands
E-mail: h.scheffer@medgen.azg.nl
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Scheffer, H., Cobben, J., Matthijs, G. et al. Best practice guidelines for molecular analysis in spinal muscular atrophy. Eur J Hum Genet 9, 484–491 (2001). https://doi.org/10.1038/sj.ejhg.5200667
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DOI: https://doi.org/10.1038/sj.ejhg.5200667
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