European Journal of Human Genetics - Clinical Utility Gene Card for: 3-M syndrome - Update 2013

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European Journal of Human Genetics - Clinical Utility Gene Card for: 3-M syndrome - Update 2013

Clinical Utility Gene Card Update

European Journal of Human Genetics advance online publication 31 July 2013; doi: 10.1038/ejhg.2013.156

Clinical Utility Gene Card for: 3-M syndrome - Update 2013

Muriel Holder-Espinasse¹, Melita Irving¹ and Valérie Cormier-Daire²

1. ¹Department of Clinical Genetics, Guy's Hospital, London, UK


2. ²Département de Génétique, Université Paris Descartes, INSERM U781, Hôpital Necker Enfants Malades, Paris, France

Correspondence: Dr M Holder-Espinasse, Department of Clinical Genetics, 7th Floor Borough Wing, Guy’s Hospital, London SE1 9RT, UK. Tel: +44 20 71881362; Fax: +44 20 71881369; E-mail: muriel.holder@gstt.nhs.uk

Update to: European Journal of Human Genetics (2011) 19,31 July 2013; doi:10.1038/ejhg.2011.32; published online 2 March 2011

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1. DISEASE CHARACTERISTICS

1.1 Name of the disease (synonyms)

3-M syndrome (gloomy face syndrome, dolichospondylic dysplasia).

1.2 OMIM# of the disease

273750.

1.3 Name of the analysed genes or DNA/chromosome segments

CUL7, OBSL1 and CCDC8.

1.4 OMIM# of the gene(s)

609577 (CUL7), 610991 (OBSL1) and 614145 (CCDC8).

1.5 Mutational spectrum

CUL7: predominance of null mutations (nonsense and splice site but missense also frequent). Fifty percent of CUL7 mutations are located in the cullin domain critical for anchoring the ROC1 protein; the others are located throughout the gene. Major gene involved in 75% of 3-M cases. OBSL1: mutations within the first eight exons affecting all known isoforms, with a predominance of loss-of-function mutations. Prevalent mutation c.1273insA (p.T245fs*40) identified in 12/23 families with OBSL1 mutations. CCDC8: comprises a single exon. Mutations generate truncated CCDC8 with subsequent loss of function.