In a Vietnamese population, MSX1 variants contribute to cleft lip and palate

Suzuki, Yasushi; Jezewski, Peter A.; Machida, Junichiro; Watanabe, Yoriko; Shi, Min; Cooper, Margaret E.; Viet, Le Thi; Tin, Nguyen Thi Duc; Hai, Huynh Dai; Natsume, Nagato; Shimozato, Kazuo; Marazita, Mary L.; Murray, Jeffrey C.

doi:10.1097/01.gim.0000127275.52925.05

Cited by 101 publications

(117 citation statements)

References 25 publications

(29 reference statements)

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“…Of these variants, only the P147Q variant, which has been detected in a number of Southeast Asian populations, is a relatively common variation in the MSX1 gene. In addition to the present study, this variant has been detected in three Vietnamese families, 17 two Filipino families 9 and three Thai families. 26 The prevalence of this variant may reflect a Founder effect in these populations.…”

Section: Discussionsupporting

confidence: 68%

“…Several studies using MSX1-CA and TGFB3-CA markers have found significant associations with non-syndromic orofacial cleft, 7,17,18 whereas others have found no significant association. 8,11,19,20 In the present research, no transmission distortion was found in the transmission disequilibrium analysis for either MSX1-CA or TGFB3-CA intragenic markers, but TGFB3-CA exhibited a trend to excess maternal transmission.…”

Section: Discussionmentioning

confidence: 96%

“…Consistent with the present study, it has been detected across affected and non-affected members of the same family and in unrelated healthy controls. 9,17,26 Although this variant is located within a conserved phosphorylation motif within the MH3 domain, 23 it is revealed that it may not be pathogenic. 26 Therefore, it, at best, may contribute to clefting with other genetic and environmental risk factors in a complex inheritance pattern.…”

Section: Discussionmentioning

confidence: 99%

“…In spite of a significant association between non-syndromic orofacial clefts and MSX1, previous studies have not identified clear Mendelian inheritance or a genotype-phenotype correlation. 17,22,26 In contrast to the tooth agenesis, most of the MSX1 mutations that have been identified among non-syndromic clefts cases are found outside the most highly conserved homeodomain. 17,22,26 Similar to other studies, we have found three variants without clear Mendelian inheritance in single-cleft cases.…”

Section: Discussionmentioning

confidence: 99%

“…17,22,26 In contrast to the tooth agenesis, most of the MSX1 mutations that have been identified among non-syndromic clefts cases are found outside the most highly conserved homeodomain. 17,22,26 Similar to other studies, we have found three variants without clear Mendelian inheritance in single-cleft cases. Of these variants, only the P147Q variant, which has been detected in a number of Southeast Asian populations, is a relatively common variation in the MSX1 gene.…”

Section: Discussionmentioning

confidence: 99%

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Contribution of MSX1 variants to the risk of non-syndromic cleft lip and palate in a Malay population

et al. 2011

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Oral clefts are clinically and genetically heterogeneous disorders that are influenced by both genetic and environmental factors. The present family-based association study investigated the role of the MSX1 and TGFB3 genes in the etiology of non-syndromic oral cleft in a Malay population. No transmission distortion was found in the transmission disequilibrium analysis for either MSX1-CA or TGFB3-CA intragenic markers, whereas TGFB3-CA exhibited a trend to excess maternal transmission. In sequencing the MSX1 coding regions in 124 patients with oral cleft, five variants were found, including three known variants (A34G, G110G and P147Q) and two novel variants (M37L and G267A). The P147Q and M37L variants were not observed in 200 control chromosomes, whereas G267A was found in one control sample, indicating a very rare polymorphic variant. Furthermore, the G110G variant displayed a significant association between patients with non-syndromic cleft lip, with or without cleft palate, and normal controls (P¼0.001, odds ratio¼2.241, 95% confidence interval, 1.357-3.700). Therefore, these genetic variants may contribute, along with other genetic and environmental factors, to this condition. INTRODUCTIONOral clefts are clinically and genetically heterogeneous disorders, involving both genetic and environmental factors. MSX1 and TGFB3 have emerged as candidate genes for oral cleft, based on expression studies 1,2 and animal models. 3,4 Their involvement is further supported by linkage and association studies in populations of different ethnic origin. [5][6][7][8] Although no deleterious mutation has been reported in TGFB3. 7,9 MSX1 has been suggested to function upstream of TGFB3 in the development of oral cleft. 10 The aim of the current research was to investigate the genetic association of MSX1 and TGFB3 in a Malay population with non-syndromic orofacial cleft. The association study was performed using intragenic CA markers for MSX1 and TGFB3. The coding regions of MSX1 were also directly sequenced.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Contribution of MSX1 variants to the risk of non-syndromic cleft lip and palate in a Malay population

et al. 2011

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CHD7 gene and non‐syndromic cleft lip and palate

Félix¹,

Hanshaw²,

Mueller³

et al. 2006

American J of Med Genetics Pt A

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Cleft lip and palate is a common birth defect that has a complex etiology resulting from an interaction of genetic and environmental factors. Few genes are known to contribute to its etiology. CHARGE syndrome is a common multiple malformation syndrome in which 20-36% of the cases have clefting. CHARGE is caused by mutations or deletions in the CHD7 gene. We analyzed the coding regions of CHD7 in nine CHARGE cases and identified five mutations, four of which were novel. We sequenced selected CHD7 exons in non-syndromic clefting cases from Iowa and Philippines populations, as well as matched controls. Variants in nonsyndromic cases were found, however, the numbers were not statistically different from the controls. Association analysis of three single nucleotide polymorphisms (SNPs) using 878 case-parent triads from Iowa and Philippines population showed no significant overtransmission. Mutations in CHD7 are not common in isolated clefting cases and we found minimal evidence that CHD7 can act as a modifier for non-syndromic clefting. ß 2006 Wiley-Liss, Inc.

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PVRL1 variants contribute to non‐syndromic cleft lip and palate in multiple populations

Avila¹,

Jezewski²,

Vieira³

et al. 2006

American J of Med Genetics Pt A

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Poliovirus Receptor Like-1 (PVRL1) is a member of the immunoglobulin super family that acts in the initiation and maintenance of epithelial adherens junctions and is mutated in the cleft lip and palate/ectodermal dysplasia 1 syndrome (CLPED1, OMIM #225000). In addition, a common nonsense mutation in PVRL1 was discovered more often among non-syndromic sporadic clefting cases in Northern Venezuela in a previous case-control study. The present work sought to ascertain the role of PVRL1 in the sporadic forms of orofacial clefting in multiple populations. Multiple rare and common variants from all three splice isoforms were initially ascertained by sequencing 92 Iowan and 86 Filipino cases and CEPH controls. Using a family-based analysis to examine these variants, the common glycine allele of the G361V coding variant was significantly overtransmitted among all orofacial clefting phenotypes (P = 0.005). This represented G361V genotyping from over 800 Iowan, Danish, and Filipino families. Among four rare amino acid changes found within the V1 and C1 domains, S112T and T131A were found adjacent to critical amino acid positions within the V1 variable domain, regions previously shown to mediate cell-to-cell and cell-to-virus adhesion. The T131A variant was not found in over 1,300 non-affected control samples although the alanine is found in other species. The serine of the S112T variant position is conserved across all known PVRL1 sequences. Together these data suggest that both rare and common mutations within PVRL1 make a minor contribution to disrupting the initiation and regulation of cell-to-cell adhesion and downstream morphogenesis of the embryonic face.

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In a Vietnamese population, MSX1 variants contribute to cleft lip and palate

Cited by 101 publications

References 25 publications

Contribution of MSX1 variants to the risk of non-syndromic cleft lip and palate in a Malay population

Contribution of MSX1 variants to the risk of non-syndromic cleft lip and palate in a Malay population

CHD7 gene and non‐syndromic cleft lip and palate

PVRL1 variants contribute to non‐syndromic cleft lip and palate in multiple populations

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