Study of four genes belonging to the folate pathway: transcobalamin 2 is involved in the onset of non-syndromic cleft lip with or without cleft palate

Cleft lip with or without cleft palate (CL/P) is the most common inborn craniofacial anomaly. Affected individuals require extensive medical and psychosocial support. Although CL/P has a complex and poorly understood etiology, increasing evidence of folate pathway involvement has been collected. So...

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Published inHuman mutation Vol. 27; no. 3; p. 294
Main Authors Martinelli, Marcella, Scapoli, Luca, Palmieri, Annalisa, Pezzetti, Furio, Baciliero, Ugo, Padula, Ernesto, Carinci, Paolo, Giovanni Morselli, Paolo, Carinci, Francesco
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.03.2006
Hindawi Limited
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Summary:Cleft lip with or without cleft palate (CL/P) is the most common inborn craniofacial anomaly. Affected individuals require extensive medical and psychosocial support. Although CL/P has a complex and poorly understood etiology, increasing evidence of folate pathway involvement has been collected. So far, only the MTHFR gene has been extensively investigated as a risk factor for CL/P, while little has been done to test genetic variations in the folate biosynthetic pathways that may influence the infant's susceptibility to these birth defects. To date, this paper presents the first attempt to verify the involvement of four genes belonging to the folate pathway in nonsyndromic cleft onset. We used a case‐parent triad design to test for linkage disequilibrium in the case of seven SNPs mapping on four different genes: transcobalamin 1 and 2 (TCN1 and TCN2), methionine synthase (MTR), and MTR reductase (MTRR). Our finding suggests that TCN2 is involved in causing CL/P. Indeed, significant overtransmission of the C allele was observed at the polymorphism c.776C>G (p.Pro259Arg) to the affected offspring (P=0.01). Results obtained with additional TCN2 polymorphisms suggest that c.776C>G may be functionally related to CL/P. However, because conflicting data exist with regard to the effect of the polymorphism in transcobalamin 2 function or in perturbing plasma levels of key molecules in the folate pathway, further investigation is warranted to confirm our data. © 2006 Wiley‐Liss, Inc.
Bibliography:Communicated by Andrew O. M. Wilkie
Online Citation: Human Mutation, Mutation in Brief #882 (2006) Online http://www3.interscience.wiley.com/homepages/38515/pdf/882.pdf
istex:C320B64FE073859B82970C5779F0329183DA5207
Fondazione TeleThon - No. GGP05147
Fondazione CARIVERONA - No. 147
ark:/67375/WNG-CH7Q86CC-T
ArticleID:HUMU9411
Human Mutation
http://www3.interscience.wiley.com/homepages/38515/pdf/882.pdf
Online Citation
Mutation in Brief #882 (2006) Online
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1059-7794
1098-1004
DOI:10.1002/humu.9411