Role of TBX1 in human del22q11.2 syndrome.
Background: Del22q11.2 syndrome is the most frequent known chromosomal microdeletion syndrome, with an incidence of 1 in 4000-5000 livebirths. It is characterised by a 3-Mb deletion on chromosome 22q11.2, cardiac abnormalities, T-cell deficits, cleft palate facial anomalies, and hypocalcaemia. At le...
| Publicado en: | Lancet Vol. 362; no. 9393; pp. 1366 - 1374 |
|---|---|
| Autores principales: | , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Lancet
10/25/2003
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=136967286&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 136967286 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 01406736 LAN jtl: Lancet issn: 01406736 maglogo: N pubinfo: dt: 10/25/2003 vid: 362 iid: 9393 pid: 1297 pub: Lancet place: Philadelphia, Pennsylvania artinfo: ui: 136967286 11163925 NLM14585638 136967286 10.1016/s0140-6736(03)14632-6 NLM14585638 136967286 ppf: 1366 ppct: 8 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Role of TBX1 in human del22q11.2 syndrome. aug: au: Yagi, Hisato Furutani, Yoshiyuki Hamada, Hiromichi Sasaki, Takashi Asakawa, Shuichi Minoshima, Shinsei Ichida, Fukiko Joo, Kunitaka Kimura, Misa Imamura, Shin-ichiro Kamatani, Naoyuki Momma, Kazuo Takao, Atsuyoshi Nakazawa, Makoto Shimizu, Nobuyoshi Matsuoka, Rumiko affil: Division of Genomic Medicine, Institute of Advanced Biomedical Engineering and Science, Graduate School of Medicine, Tokyo Women's Medical University, Tokyo, Japan sug: subj: Mutation Chromosomes DiGeorge Syndrome Proteins In Situ Hybridization, Fluorescence Heart Defects, Congenital Human Phenotype Abnormalities, Multiple Female Male Validation Studies Comparative Studies Evaluation Research Multicenter Studies Female Male ab: Background: Del22q11.2 syndrome is the most frequent known chromosomal microdeletion syndrome, with an incidence of 1 in 4000-5000 livebirths. It is characterised by a 3-Mb deletion on chromosome 22q11.2, cardiac abnormalities, T-cell deficits, cleft palate facial anomalies, and hypocalcaemia. At least 30 genes have been mapped to the deleted region. However, the association of these genes with the cause of this syndrome is not clearly understood.Methods: To test for the chromosomal deletion at 22q11.2, we did fluorescence in-situ hybridisation analysis with ten probes on 22q11.2 in 235 unrelated patients with clinically diagnosed del22q11.2 syndrome. To investigate mutations in the coding sequence of TBX1, we also did genetic analysis in 13 patients from ten families who have the 22q11.2 syndrome phenotype but no detectable deletion of 22q11.2.Findings: 96% (225 of 235) of patients had a defined 1.5-3-Mb deletion at 22q11.2. We identified three mutations of TBX1 in two unrelated patients without the 22q11.2 deletion-one with sporadic conotruncal anomaly face syndrome/velocardiofacial syndrome and one with sporadic DiGeorge's syndrome-and in three patients from a family with conotruncal anomaly face syndrome/velocardiofacial syndrome. We did not record these three mutations in 555 healthy controls (1110 chromosomes; p<0.0001).Interpretation: Our results suggest that the TBX1 mutation is responsible for five major phenotypes in del22q11.2 syndrome. Therefore, we conclude that TBX1 is a major genetic determinant of the del22q11.2 syndrome. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|