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

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Abstract
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.
Keywords
ELN, Elastin, Autosomal dominant cutis laxa, Genotype, Phenotype, EHLERS-DANLOS-SYNDROME, C-TERMINAL EXTENSION, ELASTIN GENE, MUTATION, FORM, DISEASE, DERMATOSPARAXIS, TROPOELASTIN, DEGRADATION, PROCOLLAGEN

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MLA
Hadj-Rabia, Smail et al. “Twenty Patients Including 7 Probands with Autosomal Dominant Cutis Laxa Confirm Clinical and Molecular Homogeneity.” ORPHANET JOURNAL OF RARE DISEASES 8 (2013): n. pag. Print.
APA
Hadj-Rabia, S., Callewaert, B., Bourrat, E., Kempers, M., Plomp, A. S., Layet, V., Bartholdi, D., et al. (2013). Twenty patients including 7 probands with autosomal dominant cutis laxa confirm clinical and molecular homogeneity. ORPHANET JOURNAL OF RARE DISEASES, 8.
Chicago author-date
Hadj-Rabia, Smail, Bert Callewaert, Emmanuelle Bourrat, Marlies Kempers, Astrid S Plomp, Valerie Layet, Deborah Bartholdi, et al. 2013. “Twenty Patients Including 7 Probands with Autosomal Dominant Cutis Laxa Confirm Clinical and Molecular Homogeneity.” Orphanet Journal of Rare Diseases 8.
Chicago author-date (all authors)
Hadj-Rabia, Smail, Bert Callewaert, Emmanuelle Bourrat, Marlies Kempers, Astrid S Plomp, Valerie Layet, Deborah Bartholdi, Marjolijn Renard, Julie De Backer, Fransiska Malfait, Olivier Vanakker, Paul Coucke, Anne De Paepe, and Christine Bodemer. 2013. “Twenty Patients Including 7 Probands with Autosomal Dominant Cutis Laxa Confirm Clinical and Molecular Homogeneity.” Orphanet Journal of Rare Diseases 8.
Vancouver
1.
Hadj-Rabia S, Callewaert B, Bourrat E, Kempers M, Plomp AS, Layet V, et al. Twenty patients including 7 probands with autosomal dominant cutis laxa confirm clinical and molecular homogeneity. ORPHANET JOURNAL OF RARE DISEASES. 2013;8.
IEEE
[1]
S. Hadj-Rabia et al., “Twenty patients including 7 probands with autosomal dominant cutis laxa confirm clinical and molecular homogeneity,” ORPHANET JOURNAL OF RARE DISEASES, vol. 8, 2013.
@article{3157885,
  abstract     = {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.},
  articleno    = {36},
  author       = {Hadj-Rabia, Smail and Callewaert, Bert and Bourrat, Emmanuelle and Kempers, Marlies and Plomp, Astrid S and Layet, Valerie and Bartholdi, Deborah and Renard, Marjolijn and De Backer, Julie and Malfait, Fransiska and Vanakker, Olivier and Coucke, Paul and De Paepe, Anne and Bodemer, Christine},
  issn         = {1750-1172},
  journal      = {ORPHANET JOURNAL OF RARE DISEASES},
  keywords     = {ELN,Elastin,Autosomal dominant cutis laxa,Genotype,Phenotype,EHLERS-DANLOS-SYNDROME,C-TERMINAL EXTENSION,ELASTIN GENE,MUTATION,FORM,DISEASE,DERMATOSPARAXIS,TROPOELASTIN,DEGRADATION,PROCOLLAGEN},
  language     = {eng},
  pages        = {8},
  title        = {Twenty patients including 7 probands with autosomal dominant cutis laxa confirm clinical and molecular homogeneity},
  url          = {http://dx.doi.org/10.1186/1750-1172-8-36},
  volume       = {8},
  year         = {2013},
}

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