| Genotype-phenotype analysis of TCF4 mutations causing Pitt-Hopkins syndrome shows increased seizure activity with missense mutations. | |
| | |
MedLine Citation:
|
PMID: 19938247 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
PURPOSE: Pitt-Hopkins syndrome is characterized by severe mental retardation, characteristic dysmorphic features, and susceptibility to childhood-onset seizures and intermittent episodes of hyperventilation. This syndrome is caused by haploinsufficiency of TCF4, which encodes a basic helix-loop-helix transcription factor. Missense, nonsense, splice-site mutations, and gene deletions have been found in individuals with Pitt-Hopkins syndrome. Previous reports have suggested that the Pitt-Hopkins syndrome phenotype is independent of mutation or deletion type. METHODS: We screened 13,186 individuals with microarray-based comparative genomic hybridization. We also conducted a review of the literature and statistical analysis of the phenotypic features for all individuals with confirmed mutations or deletions of TCF4. RESULTS: We identified seven individuals with TCF4 deletions. All patients have features consistent with Pitt-Hopkins syndrome, although only three have breathing anomalies, and none has seizures. Our review of previously reported cases with TCF4 mutations and deletions showed that all patients with Pitt-Hopkins syndrome reported to date have severe psychomotor retardation, the onsets of seizures and hyperventilation episodes are limited to the first decade in most reported patients with Pitt-Hopkins syndrome, hyperventilation episodes are more common than seizures and are seen in the oldest patients, and individuals with missense TCF4 mutations are more likely to develop seizures. CONCLUSIONS: On the basis of an analysis of published cases, we propose a genotype-phenotype correlation of increased seizure activity with missense TCF4 mutations. |
| | |
Authors:
|
Jill A Rosenfeld; Kathleen Leppig; Blake C Ballif; Heidi Thiese; Christine Erdie-Lalena; Erwati Bawle; Sujatha Sastry; J Edward Spence; Anne Bandholz; Urvashi Surti; Jonathan Zonana; Kory Keller; Wendy Meschino; Bassem A Bejjani; Beth S Torchia; Lisa G Shaffer |
Related Documents
:
|
16582077 - Exonic stk11 deletions are not a rare cause of peutz-jeghers syndrome. 8937767 - Exclusion of treacher collins franceschetti syndrome in a subject with tetralogy of fal... 15670717 - 3beta-hydroxysterol delta7-reductase and the smith-lemli-opitz syndrome. 18349467 - Goitre and hearing impairment in a patient with pendred syndrome. 19786987 - Nutritional programming of the metabolic syndrome. 16177707 - Comparison of syndromic surveillance and a sentinel provider system in detecting an inf... |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Genetics in medicine : official journal of the American College of Medical Genetics Volume: 11 ISSN: 1530-0366 ISO Abbreviation: Genet. Med. Publication Date: 2009 Nov |
Date Detail:
|
Created Date: 2009-11-17 Completed Date: 2010-01-13 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9815831 Medline TA: Genet Med Country: United States |
Other Details:
|
Languages: eng Pagination: 797-805 Citation Subset: IM |
Affiliation:
|
Signature Genomic Laboratories, 2820 N. AstorStreet, Spokane, WA 99207, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
/
genetics* Child Female Genotype Humans Male Mental Retardation / genetics*, physiopathology* Mutation, Missense* Phenotype Seizures / genetics*, physiopathology* Sequence Deletion Syndrome Transcription Factors / genetics* |
| Chemical | |
Reg. No./Substance:
|
0/Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; 0/TCF4 protein, human; 0/Transcription Factors |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: FG syndrome, an X-linked multiple congenital anomaly syndrome: the clinical phenotype and an algorit...
Next Document: Dental professionals' knowledge about treatment of patients with spinal cord injury.