English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  A novel ALDH5A1 mutation is associated with succinic semialdehyde dehydrogenase deficiency and severe intellectual disability in an Iranian family

Puettmann, L., Stehr, H., Garshasbi, M., Hu, H., Kahrizi, K., Lipkowitz, B., et al. (2013). A novel ALDH5A1 mutation is associated with succinic semialdehyde dehydrogenase deficiency and severe intellectual disability in an Iranian family. American Journal of Medical Genetics Part A, 161A(8), 1915-1922. doi:10.1002/ajmg.a.36030.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0018-EAD0-2 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0018-EAD3-B
Genre: Journal Article

Files

show Files
hide Files
:
Püttmann.pdf (Publisher version), 2MB
Name:
Püttmann.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2013 Wiley Periodicals, Inc.
License:
-

Locators

show

Creators

show
hide
 Creators:
Puettmann, L.1, Author              
Stehr, H.2, Author              
Garshasbi, M.3, Author              
Hu, H.3, Author              
Kahrizi, K., Author
Lipkowitz, B.1, Author              
Jamali, P., Author
Tzschach, A.3, Author
Najmabadi, H., Author
Ropers, H. H.3, Author              
Musante, L.1, Author              
Kuss, A. W.1, Author              
Affiliations:
1Familial Cognitive Disorders (Luciana Musante), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestr. 73, 14195 Berlin, Germany, ou_1479644              
2Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestr, 73, 14195 Berlin, Germany, ou_1433554              
3Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestr, 73, 14195 Berlin, Germany, ou_1433549              

Content

show
hide
Free keywords: SSADH deficiency; ALDH5A1; intellectual disability; Iranian; autosomal recessive Succinate-Semialdehyde Dehydrogenase/blood/deficiency/genetics Young Adult
 Abstract: Succinic semialdehyde dehydrogenase (SSADH) deficiency is a disorder of the catabolism of the neurotransmitter gamma-aminobutyric acid (GABA) with a very variable clinical phenotype ranging from mild intellectual disability to severe neurological defects. We report here on a large Iranian family with four affected patients presenting with severe intellectual disability, developmental delay and generalized tonic-clonic seizures. Molecular genetic analysis revealed a missense mutation c.901A>G (p.K301E, RefSeq number NM_001080) in ALDH5A1 co-segregating with the disease in the family. The missense mutation affects an amino acid residue that is highly conserved across the animal kingdom. Protein modeling showed that p.K301E most likely leads to a loss of NAD(+) binding and a predicted decrease in the free energy by 6.67 kcal/mol furthermore suggests a severe destabilization of the protein. In line with these in silico observations, no SSADH enzyme activity could be detected in patient lymphoblasts.

Details

show
hide
Language(s): eng - English
 Dates: 2013-07-042013-08
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1002/ajmg.a.36030
ISSN: 1552-4833 (Electronic)1552-4825 (Print)
URI: http://www.ncbi.nlm.nih.gov/pubmed/23825041
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: American Journal of Medical Genetics Part A
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Hoboken, N.J. : Wiley-Liss
Pages: - Volume / Issue: 161A (8) Sequence Number: - Start / End Page: 1915 - 1922 Identifier: ISSN: 1552-4825
CoNE: /journals/resource/954925476465