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Conference Paper: Identification of 7 novel transforming growth factor β receptor 2 mutations in Chinese patients with marfan syndrome

TitleIdentification of 7 novel transforming growth factor β receptor 2 mutations in Chinese patients with marfan syndrome
Authors
Issue Date2008
PublisherAmerican Academy of Pediatrics. The Journal's web site is located at http://pediatrics.aappublications.org/
Citation
The 25th International Congress of Pediatrics, Athens, Greece, 25-30 August 2007. In Pediatrics, 2008, v. 121 suppl. 2, p. s116 How to Cite?
AbstractINTRODUCTION: Marfan syndrome (MFS) (Online Mendelian Inheritance in Man [OMIM] No. 154700) is an autosomal-dominant connective tissue disorder that affects multiple systems including the cardiovascular, ocular, and musculoskeletal systems. Fibrillin 1 (FBN1) (OMIM No. 134797) mutations are causative in _90% of the cases, and recent studies have shown that transforming growth factor receptor 2 (TGFBR2) (OMIM No. 190182) mutations could be identified in 10% of non-FBN1 probands (Ma´tya´s G, Arnold E, Carrel T, et al. Hum Mutat. 2006;27:760–769). OBJECTIVE: Our objective was to examine the mutation spectrum of TGFBR2 in non-FBN1 Chinese patients with MFS and related phenotypes. METHODS: All Chinese probands who were referred for evaluation of MFS and tested negative for FBN1 mutations were included. Mutational screening was performed by denaturing high-pressure liquid chromatography (Kosaki K, Udaka T, Okuyama T. Mol Genet Metab. 2005;86:117–123). Amplicons with an abnormal elution pattern were selected for direct sequencing. RESULTS: Seven novel mutations were identified in 7 of 41 probands. All of them had prominent cardioskeletal phenotypes without ocular or dural involvement, which confirmed previous findings (Disabella E, Grasso M, Marziliano N, et al: Eur J Hum Genet. 2006;14;34–38). Six mutations were missense (R190H, D247V, T325P, G357R, I510N, and T530I), and 1 was frameshift (P501fsX17). Except for R190H, all were found in the functionally important kinase domain. Bioinformatic analyses showed that (1) all mutations occurred in conserved positions by cross-species comparison between 6 orthologs, and (2) R190H, T325P, T530I, and G357R were also found in conserved positions among 3 paralogs (TGFBR1 and activin receptors AVR2A and AVR2B) in the TGFBR superfamily. None of the 7 were found in 50 unaffected individuals (100 normal alleles). With the TGFBR2 mutations, 4 additional probands would fulfill the diagnostic criteria of MFS. CONCLUSIONS: TGFBR2 mutation was identified in 17% of our non-FBN1 probands. It should be considered in the evaluation for MFS after FBN1 screening, especially if there are compatible clinical features.
DescriptionThis journal suppl. entitled: Abstracts of the 25th International Congress of Pediatrics, August 25–30, 2007, Athens, Greece
Session - Genetics
Persistent Identifierhttp://hdl.handle.net/10722/106300
ISSN
2015 Impact Factor: 5.196
2015 SCImago Journal Rankings: 3.226

 

DC FieldValueLanguage
dc.contributor.authorChung, BHY-
dc.contributor.authorLi, YH-
dc.contributor.authorLam, STS-
dc.contributor.authorYang, W-
dc.contributor.authorLun, KS-
dc.contributor.authorLau, YL-
dc.date.accessioned2010-09-25T23:09:59Z-
dc.date.available2010-09-25T23:09:59Z-
dc.date.issued2008-
dc.identifier.citationThe 25th International Congress of Pediatrics, Athens, Greece, 25-30 August 2007. In Pediatrics, 2008, v. 121 suppl. 2, p. s116-
dc.identifier.issn0031-4005-
dc.identifier.urihttp://hdl.handle.net/10722/106300-
dc.descriptionThis journal suppl. entitled: Abstracts of the 25th International Congress of Pediatrics, August 25–30, 2007, Athens, Greece-
dc.descriptionSession - Genetics-
dc.description.abstractINTRODUCTION: Marfan syndrome (MFS) (Online Mendelian Inheritance in Man [OMIM] No. 154700) is an autosomal-dominant connective tissue disorder that affects multiple systems including the cardiovascular, ocular, and musculoskeletal systems. Fibrillin 1 (FBN1) (OMIM No. 134797) mutations are causative in _90% of the cases, and recent studies have shown that transforming growth factor receptor 2 (TGFBR2) (OMIM No. 190182) mutations could be identified in 10% of non-FBN1 probands (Ma´tya´s G, Arnold E, Carrel T, et al. Hum Mutat. 2006;27:760–769). OBJECTIVE: Our objective was to examine the mutation spectrum of TGFBR2 in non-FBN1 Chinese patients with MFS and related phenotypes. METHODS: All Chinese probands who were referred for evaluation of MFS and tested negative for FBN1 mutations were included. Mutational screening was performed by denaturing high-pressure liquid chromatography (Kosaki K, Udaka T, Okuyama T. Mol Genet Metab. 2005;86:117–123). Amplicons with an abnormal elution pattern were selected for direct sequencing. RESULTS: Seven novel mutations were identified in 7 of 41 probands. All of them had prominent cardioskeletal phenotypes without ocular or dural involvement, which confirmed previous findings (Disabella E, Grasso M, Marziliano N, et al: Eur J Hum Genet. 2006;14;34–38). Six mutations were missense (R190H, D247V, T325P, G357R, I510N, and T530I), and 1 was frameshift (P501fsX17). Except for R190H, all were found in the functionally important kinase domain. Bioinformatic analyses showed that (1) all mutations occurred in conserved positions by cross-species comparison between 6 orthologs, and (2) R190H, T325P, T530I, and G357R were also found in conserved positions among 3 paralogs (TGFBR1 and activin receptors AVR2A and AVR2B) in the TGFBR superfamily. None of the 7 were found in 50 unaffected individuals (100 normal alleles). With the TGFBR2 mutations, 4 additional probands would fulfill the diagnostic criteria of MFS. CONCLUSIONS: TGFBR2 mutation was identified in 17% of our non-FBN1 probands. It should be considered in the evaluation for MFS after FBN1 screening, especially if there are compatible clinical features.-
dc.languageeng-
dc.publisherAmerican Academy of Pediatrics. The Journal's web site is located at http://pediatrics.aappublications.org/-
dc.relation.ispartofPediatrics-
dc.titleIdentification of 7 novel transforming growth factor β receptor 2 mutations in Chinese patients with marfan syndrome-
dc.typeConference_Paper-
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1120-7507&volume=121&spage=s116&epage=&date=2008&atitle=Identification+of+7+novel+transforming+growth+factor2+receptor+2+mutations+in+Chinese+patients+with+marfan+syndromeen_HK
dc.identifier.emailChung, BHY: bhychung@hkucc.hku.hk-
dc.identifier.emailLi, YH: sulishy@hkucc.hku.hk-
dc.identifier.emailYang, W: yangwl@hkucc.hku.hk-
dc.identifier.emailLun, KS: lunks@HKUCC.hku.hk-
dc.identifier.emailLau, YL: lauylung@hkucc.hku.hk-
dc.identifier.authorityChung, BHY=rp00473-
dc.identifier.authorityYang, W=rp00524-
dc.identifier.authorityLau, YL=rp00361-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1542/peds.2007-2022KKK-
dc.identifier.doi10.1542/peds.2007-2022LLL-
dc.identifier.hkuros141244-
dc.identifier.volume121-
dc.identifier.issuesuppl. 2-
dc.identifier.spages116-
dc.identifier.epages116-
dc.publisher.placeUnited States-

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