English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Mutations in the ZNF41 gene are associated with cognitive deficits: identification of a new candidate for X-linked mental retardation

Shoichet, S. A., Hoffmann, K., Menzel, C., Trautmann, U., Moser, B., Hoeltzenbein, M., et al. (2003). Mutations in the ZNF41 gene are associated with cognitive deficits: identification of a new candidate for X-linked mental retardation. American Journal of Human Genetics, 73(6), 1341-1354.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8972-5 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8973-3
Genre: Journal Article
Alternative Title : Am. J. Hum. Genet.

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Shoichet, Sarah A.1, Author              
Hoffmann, Kirsten2, Author
Menzel, Corinna2, Author
Trautmann, Udo, Author
Moser, Bettina2, Author
Hoeltzenbein, Maria2, Author
Echenne, Bernard, Author
van Bokhoven, Hans, Author
Moraine, Claude, Author
Fryns, Jean-Pierre, Author
Chelly, Jamel, Author
Rott, Hans-Dieter, Author
Ropers, Hans-Hilger1, Author              
Kalscheuer, Vera M.3, Author              
Affiliations:
1Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              
2Max Planck Society, ou_persistent13              
3Chromosome Rearrangements and Disease (Vera Kalscheuer), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479642              

Content

show
hide
Free keywords: -
 Abstract: Nonsyndromic X-linked mental retardation (MRX) is defined by an X-linked inheritance pattern of low IQ, problems with adaptive behavior, and the absence of additional specific clinical features. The 13 MRX genes identified to date account for less than one-fifth of all MRX, suggesting that numerous gene defects cause the disorder in other families. In a female patient with severe nonsyndromic mental retardation and a de novo balanced translocation t(X;7)(p11.3;q11.21), we have cloned the DNA fragment that contains the X-chromosomal and the autosomal breakpoint. In silico sequence analysis provided no indication of a causative role for the chromosome 7 breakpoint in mental retardation (MR), whereas, on the X chromosome, a zinc-finger gene, ZNF41, was found to be disrupted. Expression studies indicated that ZNF41 transcripts are absent in the patient cell line, suggesting that the mental disorder in this patient results from loss of functional ZNF41. Moreover, screening of a panel of patients with MRX led to the identification of two other ZNF41 mutations that were not found in healthy control individuals. A proline-to-leucine amino acid exchange is present in affected members of one family with MRX. A second family carries an intronic splice-site mutation that results in loss of specific ZNF41 splice variants. Wild-type ZNF41 contains a highly conserved transcriptional repressor domain that is linked to mechanisms of chromatin remodeling, a process that is defective in various other forms of MR. Our results suggest that ZNF41 is critical for cognitive development; further studies aim to elucidate the specific mechanisms by which ZNF41 alterations lead to MR.

Details

show
hide
Language(s): eng - English
 Dates: 2003-11
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: eDoc: 173608
ISI: 000185599702374
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: American Journal of Human Genetics
  Alternative Title : Am. J. Hum. Genet.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 73 (6) Sequence Number: - Start / End Page: 1341 - 1354 Identifier: ISSN: 0002-9297