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  Severe congenital cutis laxa with cardiovascular manifestations due to homozygous deletions in ALDH18A1

Fischer, B., Callewaert, B., Schroter, P., Coucke, P. J., Schlack, C., Ott, C. E., et al. (2014). Severe congenital cutis laxa with cardiovascular manifestations due to homozygous deletions in ALDH18A1. Molecular Genetics and Metabolism, 112(4), 310-316. doi:10.1016/j.ymgme.2014.05.003.

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© 2014 Elsevier B.V.
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 Creators:
Fischer, B.1, Author
Callewaert, B., Author
Schroter, P., Author
Coucke, P. J., Author
Schlack, C., Author
Ott, C. E., Author
Morroni, M., Author
Homann, W., Author
Mundlos, S.2, Author              
Morava, E., Author
Ficcadenti, A., Author
Kornak, U.2, Author              
Affiliations:
1Max Planck Society, ou_persistent13              
2Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              

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Free keywords: Autosomal recessive cutis laxa; ALDH18A1; Homozygous deletion 10q24.3; Progeroid features; PYCR1; Mitochondria
 Abstract: Autosomal recessive cutis laxa (ARCL) type 2 constitutes a heterogeneous group of diseases mainly characterized by lax and wrinkled skin, skeletal anomalies, and a variable degree of intellectual disability. ALDH18A1-related ARCL is the most severe form within this disease spectrum. Here we report on the clinical and molecular findings of two affected individuals from two unrelated families. The patients presented with typical features of de Barsy syndrome and an overall progeroid appearance. However, the phenotype was highly variable including cardiovascular involvement in the more severe case. Investigation of a skin biopsy of one patient revealed not only the typical alterations of elastic fibers, but also an altered structure of mitochondria in cutaneous fibroblasts. Using conventional sequencing and copy number analysis we identified a frameshift deletion of one nucleotide and a microdeletion affecting the ALDH18A1 gene, respectively, in a homozygous state in both patients. Expression analysis in dermal fibroblasts from the patient carrying the microdeletion showed an almost complete absence of the ALDH18A1 mRNA resulting in an absence of the ALDH18A1 protein. So far, only 13 affected individuals from seven unrelated families suffering from ALDH18A1-related cutis laxa have been described in literature. Our findings provide new insights into the clinical spectrum and show that beside point mutations microdeletions are a possible cause of ALDH18A1-ARCL.

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Language(s): eng - English
 Dates: 2014-05-212014-08
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.ymgme.2014.05.003
ISSN: 1096-7206 (Electronic)1096-7192 (Print)
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Title: Molecular Genetics and Metabolism
Source Genre: Journal
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Publ. Info: Orlando, FL : Academic Press
Pages: - Volume / Issue: 112 (4) Sequence Number: - Start / End Page: 310 - 316 Identifier: ISSN: 1096-7192
CoNE: https://pure.mpg.de/cone/journals/resource/954922651185