Hamid Ganji1, Mansoor Salehi2, Maryam Sedghi1, Hossein Abdali3, Nayereh Nouri1, Leyli Sadri4, Majid Hosseinzadeh5, Bahareh Vakili5, Mahdi Lotfi3. 1. Pediatric Inherited Disease Research Center (PIDRC), Isfahan University of Medical Sciences, Isfahan, Iran; Molecular Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran. 2. Molecular Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran; Division of Genetics and Molecular Biology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran. 3. Department of Plastic and Reconstructive Surgery , Alzahra University Hospital, Isfahan University of Medical Sciences , Isfahan , Iran. 4. Students' Research Center, School of Dentistry, Isfahan University of Medical Sciences , Isfahan , Iran. 5. Molecular Genetics Laboratory , Alzahra University Hospital, Isfahan University of Medical Sciences , Isfahan , Iran.
Abstract
BACKGROUND: DiGeorge syndrome (DGS) is the result of a microdeletion in chromosome 22q11.2 in over 90% of cases. DGS is the second most frequent syndrome after Down syndrome and has an incidence of 1/4000 births. Unequal crossover between low-copy repeats, on the proximal part of the long arm of chromosome 22, usually results in a 3 Mb deletion in one of the chromosome 22 and a reciprocal and similarly sized duplication on the other one. Several studies have indicated that TBX1 (T-box 1) haploinsufficiency is responsible for many of the phenotypic traits of 22q11.2 deletion syndrome. Conotruncal heart defects (CTDs) are present in 75-85% of patients with 22q11.2 deletion syndrome in Western countries. METHODS: Among 78 patients fulfilling the criteria for DGS diagnosed by the fluorescence in situ hybridisation test, 24 had 22q11.2 deletion. Screening for TBX1 gene deletion was performed by multiplex ligation-dependent probe amplification (MLPA). RESULTS: Our results revealed that of 24 patients with TBX1 gene deletion, 12 had CTDs while 12 did not show any heart defects. CONCLUSIONS: Our findings indicate that other genes or gene interactions may play a role in penetrance or the severity of heart disease among patients with DGS.
BACKGROUND:DiGeorge syndrome (DGS) is the result of a microdeletion in chromosome 22q11.2 in over 90% of cases. DGS is the second most frequent syndrome after Down syndrome and has an incidence of 1/4000 births. Unequal crossover between low-copy repeats, on the proximal part of the long arm of chromosome 22, usually results in a 3 Mb deletion in one of the chromosome 22 and a reciprocal and similarly sized duplication on the other one. Several studies have indicated that TBX1 (T-box 1) haploinsufficiency is responsible for many of the phenotypic traits of 22q11.2 deletion syndrome. Conotruncal heart defects (CTDs) are present in 75-85% of patients with 22q11.2 deletion syndrome in Western countries. METHODS: Among 78 patients fulfilling the criteria for DGS diagnosed by the fluorescence in situ hybridisation test, 24 had 22q11.2 deletion. Screening for TBX1 gene deletion was performed by multiplex ligation-dependent probe amplification (MLPA). RESULTS: Our results revealed that of 24 patients with TBX1 gene deletion, 12 had CTDs while 12 did not show any heart defects. CONCLUSIONS: Our findings indicate that other genes or gene interactions may play a role in penetrance or the severity of heart disease among patients with DGS.
Authors: Jan P Schouten; Cathal J McElgunn; Raymond Waaijer; Danny Zwijnenburg; Filip Diepvens; Gerard Pals Journal: Nucleic Acids Res Date: 2002-06-15 Impact factor: 16.971
Authors: A Rauch; K Devriendt; A Koch; R Rauch; M Gewillig; C Kraus; M Weyand; H Singer; A Reis; M Hofbeck Journal: J Med Genet Date: 2004-04 Impact factor: 6.318
Authors: S Merscher; B Funke; J A Epstein; J Heyer; A Puech; M M Lu; R J Xavier; M B Demay; R G Russell; S Factor; K Tokooya; B S Jore; M Lopez; R K Pandita; M Lia; D Carrion; H Xu; H Schorle; J B Kobler; P Scambler; A Wynshaw-Boris; A I Skoultchi; B E Morrow; R Kucherlapati Journal: Cell Date: 2001-02-23 Impact factor: 41.582
Authors: Laura Torres-Juan; Jordi Rosell; Montse Morla; Catalina Vidal-Pou; Fernando García-Algas; Maria-Angeles de la Fuente; Miguel Juan; Albert Tubau; Daniel Bachiller; Marta Bernues; Angeles Perez-Granero; Nancy Govea; Xavier Busquets; Damian Heine-Suñer Journal: Eur J Hum Genet Date: 2007-03-21 Impact factor: 4.246
Authors: Sulagna C Saitta; Stacy E Harris; Ann P Gaeth; Deborah A Driscoll; Donna M McDonald-McGinn; Melissa K Maisenbacher; Jill M Yersak; Prabir K Chakraborty; April M Hacker; Elaine H Zackai; Terry Ashley; Beverly S Emanuel Journal: Hum Mol Genet Date: 2003-12-17 Impact factor: 6.150
Authors: Thomas M Maynard; Gloria T Haskell; Jeffrey A Lieberman; Anthony-Samuel LaMantia Journal: Int J Dev Neurosci Date: 2002 Jun-Aug Impact factor: 2.457
Authors: Regina E Ensenauer; Adewale Adeyinka; Heather C Flynn; Virginia V Michels; Noralane M Lindor; D Brian Dawson; Erik C Thorland; Cindy Pham Lorentz; Jennifer L Goldstein; Marie T McDonald; Wendy E Smith; Elba Simon-Fayard; Alan A Alexander; Anita S Kulharya; Rhett P Ketterling; Robin D Clark; Syed M Jalal Journal: Am J Hum Genet Date: 2003-10-02 Impact factor: 11.025