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  Microduplications encompassing the Sonic hedgehog limb enhancer ZRS are associated with Haas-type polysyndactyly and Laurin-Sandrow syndrome

Lohan, S., Spielmann, M., Doelken, S. C., Flottmann, R., Muhammad, F., Baig, S. M., et al. (2014). Microduplications encompassing the Sonic hedgehog limb enhancer ZRS are associated with Haas-type polysyndactyly and Laurin-Sandrow syndrome. Clinical Genetics: an international journal of genetics in medicine, 86(4), 318-325. doi:10.1111/cge.12352.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-B3BA-6 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-B3BB-4
Genre: Journal Article

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© 2014 John Wiley & Sons, Inc.
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 Creators:
Lohan, S.1, Author
Spielmann, M.2, Author              
Doelken, S. C., Author
Flottmann, R., Author
Muhammad, F., Author
Baig, S. M., Author
Wajid, M., Author
Hulsemann, W., Author
Habenicht, R., Author
Kjaer, K. W., Author
Patil, S. J., Author
Girisha, K. M., Author
Abarca-Barriga, H. H., Author
Mundlos, S.2, Author              
Klopocki, E.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: CNVs; Laurin-Sandrow syndrome; microduplication; SHH; ZRS-associated syndromes
 Abstract: Laurin-Sandrow syndrome (LSS) is a rare autosomal dominant disorder characterized by polysyndactyly of hands and/or feet, mirror image duplication of the feet, nasal defects, and loss of identity between fibula and tibia. The genetic basis of LSS is currently unknown. LSS shows phenotypic overlap with Haas-type polysyndactyly (HTS) regarding the digital phenotype. Here we report on five unrelated families with overlapping microduplications encompassing the Sonic hedgehog (SHH) limb enhancer ZPA regulatory sequence (ZRS) on chromosome 7q36. Clinically, the patients show polysyndactyly phenotypes and various types of lower limb malformations ranging from syndactyly to mirror image polydactyly with duplications of the fibulae. We show that larger duplications of the ZRS region (>80 kb) are associated with HTS, whereas smaller duplications (<80 kb) result in the LSS phenotype. On the basis of our data, the latter can be clearly distinguished from HTS by the presence of mirror image polysyndactyly of the feet with duplication of the fibula. Our results expand the clinical phenotype of the ZRS-associated syndromes and suggest that smaller duplications (<80 kb) are associated with a more severe phenotype. In addition, we show that these small microduplications within the ZRS region are the underlying genetic cause of Laurin-Sandrow syndrome.

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Language(s): eng - English
 Dates: 2014-02-172014-10
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1111/cge.12352
ISSN: 1399-0004 (Electronic)0009-9163 (Print)
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Title: Clinical Genetics: an international journal of genetics in medicine
  Other : Clin. Genet.
Source Genre: Journal
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Publ. Info: Copenhagen : Munksgaard.
Pages: - Volume / Issue: 86 (4) Sequence Number: - Start / End Page: 318 - 325 Identifier: ISSN: 0009-9163
CoNE: /journals/resource/954925391292