LETTER TO JMG

Mutation analysis in the MECP2 gene and genetic counselling for Rett syndrome

H Gill¹, J P Cheadle¹, J Maynard¹, N Fleming¹, S Whatley², T Cranston³, E M Thompson⁴, H Leonard⁶, M Davis⁷, J Christodoulou⁵, O Skjeldal⁸, F Hanefeld⁹, A Kerr¹⁰, A Tandy¹¹, D Ravine¹ and A Clarke¹

¹ Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK
² Department of Medical Biochemistry, University Hospital of Wales, Heath Park, Cardiff CF14 4W, UK
³ Clinical Molecular Genetics, Level 5, Camelia Botnar Laboratories, Great Ormond Street, London WC1N 3JH, UK
⁴ South Australia Clinical Genetics Service, Women’s and Children’s Hospital, 72 King William Road, North Adelaide 5006, South Australia
⁵ Western Sydney Genetics Programme, Children’s Hospital at Westmead and Department of Paediatrics and Child Health, University of Sydney, Sydney, Australia
⁶ TVW Telethon Institute for Child Health Research, West Perth, Australia WA6872
⁷ Department of Neuropathology, Royal Perth Hospital, Perth, Australia
⁸ Department of Paediatrics, Nordland Central Hospital, N-8017 Bodo, Norway
⁹ Abteilung Kinderheilkunde, Scheuerpunk, Neuropaeditre, Georg-August-Universital, Göttingen, Germany
¹⁰ University of Glasgow, Department of Psychological Medicine, Gartnaval Royal Hospital, 1055 Great Western Road, Glasgow G12 OXH, UK
¹¹ Department of Paediatrics, Taunton and Somerset Hospital, Musgrove Park, Taunton, Somerset TA1 5DA, UK

Correspondence to:
Correspondence to:
Professor A Clarke, Department of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK;
clarkeaj@cardiff.ac.uk

Keywords: genetic counselling; MECP2; Rett syndrome

The first 150 words of the full text of this article appear below.

We looked for pathogenic MECP2 mutations in 11 families with an index case affected by Rett syndrome (RTT), together with a sib or other relative affected by RTT or a less specific developmental disturbance. In one family, we detected the same MECP2 mutation in two affected sisters and their unaffected mother, who was subsequently shown to have skewed X chromosome inactivation. In five families, one affected subject was found to have a MECP2 mutation, but the other relative in whom a diagnosis of RTT was suspected, did not carry this or any other detectable MECP2 mutation. In the remaining five families, no MECP2 mutation was detected in any subject. These results suggest that familial RTT is rare and may be overdiagnosed. Furthermore, and despite the small probability of recurrence, many relatives of females with the usual, sporadic RTT may seek genetic testing to clarify their situation.

Rett syndrome (RTT) is . . . [Full text of this article]

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