Linked Life Data

17478476

Source:http://linkedlifedata.com/resource/pubmed/id/17478476

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2007-6-4
pubmed:abstractText
Pitt-Hopkins syndrome (PHS) is a rare syndromic mental disorder, which is mainly characterized by severe motor and mental retardation including absent language development, a characteristic facial gestalt and episodes of hyperventilation. We report on a female patient with PHS showing severe mental retardation with absent speech, pronounced muscular hypotonia, ataxia, distinctive facial features, such as a coarse face, a broad nasal bridge and a wide mouth, and hyperventilation attacks. In this patient, genomic profiling by array-based comparative genomic hybridization and fluorescence in situ hybridization studies detected and confirmed a de novo 0.5 Mb deletion in 18q21.2 containing a single gene, the basic helix-loop-helix transcription factor TCF4. cDNA and genomic analyses in the patient and her parents demonstrated TCF4 haploinsufficiency as the underlying cause of the disease. Analysis of the embryonal expression pattern of the Danio rerio ortholog, tcf4, by whole-mount in situ hybridization showed a highly specific expression domain in the pallium of the telencephalon during late somitogenesis, when the patterning of the zebrafish brain is advanced and neural differentiation commences. Later expression domains were restricted to several regions in the central nervous system, including continued expression in the pallium of the telencephalon, and starting expression in the diencephalon (thalamus, ventral thalamus and posterior tuberculum), the midbrain tegmentum, the hindbrain and the branchial arches. This expression pattern correlates with the clinical phenotype. Our results show that haploinsufficiency of TCF4 causes PHS and suggest that D. rerio is a valuable model to study the molecular pathogenesis of PHS and the role of TCF4 in brain development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1488-94
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:17478476-Animals, pubmed-meshheading:17478476-Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, pubmed-meshheading:17478476-Child, pubmed-meshheading:17478476-Cytogenetic Analysis, pubmed-meshheading:17478476-DNA-Binding Proteins, pubmed-meshheading:17478476-Face, pubmed-meshheading:17478476-Female, pubmed-meshheading:17478476-Haplotypes, pubmed-meshheading:17478476-Humans, pubmed-meshheading:17478476-Hyperventilation, pubmed-meshheading:17478476-Intellectual Disability, pubmed-meshheading:17478476-Language Development Disorders, pubmed-meshheading:17478476-Models, Genetic, pubmed-meshheading:17478476-Mutation, pubmed-meshheading:17478476-Syndrome, pubmed-meshheading:17478476-TCF Transcription Factors, pubmed-meshheading:17478476-Transcription Factor 7-Like 2 Protein, pubmed-meshheading:17478476-Transcription Factors, pubmed-meshheading:17478476-Zebrafish
pubmed:year
2007
pubmed:articleTitle
Severe mental retardation with breathing abnormalities (Pitt-Hopkins syndrome) is caused by haploinsufficiency of the neuronal bHLH transcription factor TCF4.
pubmed:affiliation
1Institute of Human Genetics, Rheinische Friedrich-Wilhelms-University, 53111 Bonn, Germany.
pubmed:publicationType
Journal Article, Case Reports, Research Support, Non-U.S. Gov't