Association between alleles of the transforming growth factor‐alpha locus and the occurrence of cleft lip

Sassani, Russell; Bartlett, Scott P.; Feng, Hongshu; Goldner-Sauvé, Audrey J.; Haq, Asifa K.; Buetow, Kenneth H.; Gasser, David L.

doi:10.1002/ajmg.1320450508

Cited by 55 publications

(26 citation statements)

References 23 publications

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“…Tel : j39-0532-291538; Fax: j39-0532-291533; E-mail: tgm!unife.it located on 2p13, and the occurrence of clefting. Since then, several investigations supported a role for TGFA, or a nearby gene (OFC2), as a susceptibility gene(s) involved in some way in OFC malformations (Chenevix-Trench et al 1992 ;Holder et al 1992 ;Sassani et al 1993 ;Feng et al 1994 ;Jara et al 1995). In a recent linkage study using markers mapping on 2p13, we confirmed the genetic heterogeneity for OFC, and evidence of linkage was observed in the same group of families showing linkage to 6p23 markers .…”

Section: supporting

confidence: 77%

“…Also, many molecular genetic investigations supported major gene\oligogenic models in the development of the cleft, with evidence for loci in different chromosome regions. For example there was evidence for a locus on 6p23 (OFC1) (Eiberg et al 1987 ;Carinci et al 1995 ;Davies et al 1995 ;Scapoli et al 1997), on 2p13 (OFC2) (Ardinger et al 1989 ;Chenevix-Trench et al 1991Holder et al 1992 ;Sassani et al, 1993 ;Mitchell, 1997), 19q13 (OFC3) (Stein et al 1995 ;Wyszynski et al 1997 ;Martinelli et al 1998), on 4q25-31 (Beiraghi et al 1994 ;Healey et al 1994), and on 17q21 (RARA) (Chenevix- Trench Shaw et al 1993), all of which appeared to be involved in clefting.…”

Section: mentioning

confidence: 99%

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Linkage analysis of candidate endothelin pathway genes in nonsyndromic familial orofacial cleft

Pezzetti

Scapoli

Martinelli

et al. 2000

Annals of Human Genetics

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There is good evidence from linkage analysis and mouse model knockouts that the endothelin‐1 gene (EDN1) is a good candidate for non‐syndromic orofacial cleft (OFC) disease. EDN1 maps to the chromosomal region of the OFC1 locus in 6p23. Therefore we have examined three other candidate genes in the endothelin pathway (ECE1, EDNRA and EDNRB, which map to chromosomes 1, 4 and 13 respectively) in a linkage study of 9 families with OFC, where the disorder is not linked to chromosome 6p23. The total lod score for these 9 multiplex families never exceeded −2.00 and thus our data suggest that EDN1 and related genes are not involved in non‐syndromic familial OFC.

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Section: supporting

confidence: 77%

Section: mentioning

confidence: 99%

Linkage analysis of candidate endothelin pathway genes in nonsyndromic familial orofacial cleft

Pezzetti

Scapoli

Martinelli

et al. 2000

Annals of Human Genetics

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“…The association of the TFGa alleles with CL(P) has been confirmed by others (e.g., Chenevix-Trench et al, 1991;Holder et al, 1992;Sassani et al, 1993). ChenevixTrench et al (1992) also found an association between CL(P) and altered frequency of different RARa alleles, as did Shaw et al (1993).…”

Section: ) Genetic Factors (A) Role Of Genetic Factors In the Etiolomentioning

confidence: 60%

Prenatal Craniofacial Development: New Insights On Normal and Abnormal Mechanisms

Johnston

Bronsky²

1995

Critical Reviews in Oral Biology & Medicine

116

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Technical advances are radically altering our concepts of normal prenatal craniofacial development. These include concepts of germ layer formation, the establishment of the initial head plan in the neural plate, and the manner in which head segmentation is controlled by regulatory (homeobox) gene activity in neuromeres and their derived neural crest cells. There is also a much better appreciation of ways in which new cell associations are established. For example, the associations are achieved by neural crest cells primarily through ceil migration and subsequent cell interactions that regulate induction, growth, programmed cell death, etc. These interactions are mediated primarily by two groups of regulatory molecules, "growth factors" (e.g., FGF and TGFoc) and the so-called steroid/thyroid/retinoic acid superfamily. Considerable advances have been made with respect to our understanding of the mechanisms involved in primary and secondary palate formation, such as growth, morphogenetic movements, and the fusion/merging phenomenon. Much progress has been made on the mechanisms involved in the final differentiation of skeletal tissues.Molecular genetics and animal models for human malformations are providing many insights into abnormal development. A mouse model for the fetal alcohol syndrome (FAS), a mild form of holoprosencephaly, demonstrates a mid-line anterior neural plate deficiency which leads to olfactory placodes being positioned too close to the mid-line, and other secondary changes. Work on animal models for the retinoic acid syndrome (RAS) shows that there is major involvement of neural crest cells. There is also major crest cell involvement in similar syndromes, apparently including hemifacial microsomia. Later administration of retinoic acid prematurely and excessively kills ganglionic placodal cells and leads to a malformation complex virtually identical to the Treacher Collins syndrome. Most clefts of the lip and/or palate appear to have a multifactorial etiology. Genetic variations in TGFocs, RARocs, NADH dehydrogenase, an enzyme involved in oxidative metabolism, and cytochrome P-450, a detoxifying enzyme, have been implicated as contributing genetic factors. Cigarette smoking, with the attendant hypoxia, is a probable contributing environmental factor. It seems likely that few clefts involve single major genes. In most cases, the pathogenesis appears to involve inadequate contact and/or fusion of the facial prominences or palatal shelves. Specific mutations in genes for different FGF receptor molecules have been identified for achondroplasia and Crouzon's syndrome, and in a regulatory gene (Msx2) for one type of craniosynostosis. Poorly co-ordinated control of form and size of structures, or groups of structures (e.g., teeth and jaws), by regulatory genes should do much to explain the very frequent "mismatches" found in malocclusions and other dentofacial "deformities".Future directions for research, including possibilities for prevention, are discussed.

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Section: Etiology Of Ntds and Craniofacial Malformationsmentioning

confidence: 99%

“…Recognized associations include chromosomal abnormalities, Mendelian disorders, and various teratogenic agents (Gorlin et al, 1990). Recently, genetic studies have defined an association between genetic variation at the transforming growth factor-alpha locus and non-syndromic orofacial clefting (Ardinger et al, 1989;Chenevix-Trench et al, 1991Holder et al, 1992;Sassani et al, 1993;Shiang et al, 1993).There are a number of epidemiologic characteristics that are unique to craniofacial malformations. For example, it appears as if male infants have a higher incidence of cleft lip with or without cleft palate than do female infants, whereas the reverse is true for isolated cleft palate (Fraser, 1970;Emanuel et al, 1983;Shaw et al, 1991).…”

mentioning

confidence: 99%

Neural Tube and Craniofacial Defects With Special Emphasis On Folate Pathway Genes

Finnell

Greer

Barber

et al. 1998

Critical Reviews in Oral Biology & Medicine

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Neural tube and orofacial defects are common congenital malformations in humans. While etiologically heterogeneous, they are for the most part multifactorial in their pathogenesis, having both genetic and environmental components in their development. In recent years, there has been a great deal of epidemiologic evidence demonstrating that women who received multivitamins containing folic acid periconceptionally had significantly reduced occurrence and recurrence risks for producing infants with such malformations. This risk reduction is not observed in all populations, further suggestive of a genetic regulation of this phenomenon. Unfortunately, the mechanisms underlying the beneficial effects of folic acid are not wellunderstood. In this article, we review the relevant epidemiologic data on both neural tube defects and orofacial malformations, the fundamental embryological processes involved in closing the neural tube, and the development of the craniofacies, and propose a working hypothesis for susceptibility to these malformations. This hypothesis is based on the interworkings of cellular folate transport, focusing on the key elements involved in potocytosis. We propose that infants with mutations in the folate receptor alpha gene might be at increased risk for congenital anomalies due to a reduced binding affinity for 5-methyltetrahydrofolate, the physiologic form of folic acid. Various experimental approaches to test the working hypothesis are considered.Key words. Folic acid, birth defects, genetic susceptibility. Clinical DescriptionNeural tube defects (NTDs) are common congenital malformations that occur when the embryonic neural tube, which ultimately forms the brain and spinal cord, fails to close properly during the first few weeks of development. Anencephaly, which is invariably fatal, is characterized by the nearly complete degeneration of exposed anterior neural tube tissue (Hunter, 1993). The superficially "brain-like" mass of exposed tissue typically consists of collagen and connective and vascular tissue covered by an epithelial membrane (Hunter, 1993). When the brain is completely absent, the defect is referred to as holo-anencephaly, which occurs in approximately 65% of failed anterior neural tube closure (Myrianthopoulos and Melnick, 1987). A more mild malformation, meroanencephaly, involves the protrusion of the cerebrovasculosa through a partially formed skull (Myrianthopoulos and Melnick, 1987). According to Hunter (1993), approximately half of anencephalic infants are stillbirths, while the remainder live for variable periods of up to 48 hours.The other major NTD is spina bifida, which involves the protrusion of neural tissue through an opening in the vertebral arches and may occur anywhere along the length of the spinal cord. The severity of the defect can range from craniorachischisis, where the entire anterior and posterior neural tube is open, to a lesion limited to a single vertebral level. The vast majority of spina bifida lesions are found in the lumbar (42.2%) or lumbos...

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Association between alleles of the transforming growth factor‐alpha locus and the occurrence of cleft lip

Cited by 55 publications

References 23 publications

Linkage analysis of candidate endothelin pathway genes in nonsyndromic familial orofacial cleft

Linkage analysis of candidate endothelin pathway genes in nonsyndromic familial orofacial cleft

Prenatal Craniofacial Development: New Insights On Normal and Abnormal Mechanisms

Neural Tube and Craniofacial Defects With Special Emphasis On Folate Pathway Genes

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