English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Deletions of exons with regulatory activity at the DYNC1I1 locus are associated with split-hand/split-foot malformation: array CGH screening of 134 unrelated families

Tayebi, N., Jamsheer, A., Flöttmann, R., Sowinska-Seidler, A., Doelken, S. C., Oehl-Jaschkowitz, B., et al. (2014). Deletions of exons with regulatory activity at the DYNC1I1 locus are associated with split-hand/split-foot malformation: array CGH screening of 134 unrelated families. Orphanet Journal of Rare Diseases, 2014: 9:108. doi:10.1186/s13023-014-0108-6.

Item is

Files

show Files
hide Files
:
Tayebi.pdf (Copyright transfer agreement), 2MB
Name:
Tayebi.pdf
Description:
-
OA-Status:
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2014 Tayebi et al; licensee BioMed Central Ltd
License:
-

Locators

show
hide
Description:
-
OA-Status:

Creators

show
hide
 Creators:
Tayebi, N.1, Author
Jamsheer, A., Author
Flöttmann, R., Author
Sowinska-Seidler, A., Author
Doelken, S. C., Author
Oehl-Jaschkowitz, B., Author
Hülsemann, W., Author
Habenicht, R., Author
Klopocki, E.2, Author           
Mundlos, S.2, Author           
Spielmann, M.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              

Content

show
hide
Free keywords: SHFM, DLX5/6, DYNC1I1, Regulatory Mutations, eExons
 Abstract: BACKGROUND: A growing number of non-coding regulatory mutations are being identified in congenital disease. Very recently also some exons of protein coding genes have been identified to act as tissue specific enhancer elements and were therefore termed exonic enhancers or "eExons". METHODS: We screened a cohort of 134 unrelated families with split-hand/split-foot malformation (SHFM) with high resolution array CGH for CNVs with regulatory potential. RESULTS: In three families with an autosomal dominant non-syndromic SHFM phenotype we detected microdeletions encompassing the exonic enhancer (eExons) 15 and 17 of DYNC1I1. In a fourth family, who had hearing loss in addition to SHFM, we found a larger deletion of 510 kb including the eExons of DYNC1I1 and, in addition, the human brain enhancer hs1642. Exons 15 and 17 of DYNC1I1 are known to act as tissue specific limb enhancers of DLX5/6, two genes that have been shown to be associated with SHFM in mice. In our cohort of 134 unrelated families with SHFM, deletions of the eExons of DYNC1I1 account for approximately 3% of the cases, while 17p13.3 duplications were identified in 13% of the families, 10q24 duplications in 12%, and TP63 mutations were detected in 4%. CONCLUSIONS: We reduce the minimal critical region for SHFM1 to 78 kb. Hearing loss, however, appears to be associated with deletions of a more telomeric region encompassing the brain enhancer element hs1642. Thus, SHFM1 as well as hearing loss at the same locus are caused by deletion of regulatory elements. Deletions of the exons with regulatory potential of DYNC1I1 are an example of the emerging role of exonic enhancer elements and their implications in congenital malformation syndromes.

Details

show
hide
Language(s): eng - English
 Dates: 2014-07-29
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1186/s13023-014-0108-6
ISSN: 1750-1172 (Electronic)
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Orphanet Journal of Rare Diseases
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: BioMed Central
Pages: - Volume / Issue: 2014 Sequence Number: 9:108 Start / End Page: - Identifier: -