Twenty patients including 7 probands with autosomal dominant cutis laxa confirm clinical and molecular homogeneity

Orphanet Journal of Rare Diseases

Christine Bodemer⁵  Anne M De Paepe⁴  Paul J Coucke⁴  Olivier M Vanakker⁴  Fransiska Malfait⁴  Julie De Backer⁴  Marjolijn Renard⁴  Deborah Bartholdi⁶  Valerie Layet⁷  Astrid S Plomp²  Marlies Kempers³  Emmanuelle Bourrat¹  Bert L Callewaert⁴  Smail Hadj-Rabia⁵ 

[1] Service de Dermatologie, MAGEC Hôpital Saint-Louis, Paris, France;Academic Medical Center, Amsterdam, the Netherlands;University Medical Center St. Radboud, Nijmegen, the Netherlands;Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, B-9000, Ghent, Belgium;Service de Dermatologie – Centre de référence national des Maladies Génétiques à Expression Cutanée (MAGEC), INSERM U781, Hôpital Necker - Enfants Malades, Université Paris V-Descartes, 149, rue de Sèvres 75743 Paris Cedex 15, Paris, France;Institute of Medical Genetics, University of Zürich, Zürich, Switzerland;Groupe Hospitalier Du Havre – Department of Medical Genetics, Le Havre, France

关键词: Phenotype;    Genotype;    Autosomal dominant cutis laxa;    ELN;    Elastin;   

Others  :  864093
DOI  :  10.1186/1750-1172-8-36

 received in 2012-11-27, accepted in 2013-02-14,  发布年份 2013

【 摘 要 】

Background

Elastin gene mutations have been associated with a variety of phenotypes. Autosomal dominant cutis laxa (ADCL) is a rare disorder that presents with lax skin, typical facial characteristics, inguinal hernias, aortic root dilatation and pulmonary emphysema. In most patients, frameshift mutations are found in the 3’ region of the elastin gene (exons 30-34) which result in a C-terminally extended protein, though exceptions have been reported.

Methods

We clinically and molecularly characterized the thus far largest cohort of ADCL patients, consisting of 19 patients from six families and one sporadic patient.

Results

Molecular analysis showed C-terminal frameshift mutations in exon 30, 32, and 34 of the elastin gene and identified a mutational hotspot in exon 32 (c.2262delA). This cohort confirms the previously reported clinical constellation of skin laxity (100%), inguinal hernias (51%), aortic root dilatation (55%) and emphysema (37%).

Conclusion

ADCL is a clinically and molecularly homogeneous disorder, but intra- and interfamilial variability in the severity of organ involvement needs to be taken into account. Regular cardiovascular and pulmonary evaluations are imperative in the clinical follow-up of these patients.

【 授权许可】

   
2013 Hadj-Rabia et al; licensee BioMed Central Ltd.

【 图 表 】

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