A genome wide linkage scan for cleft lip and palate and dental anomalies

Vieira, Alexandre R.; McHenry, Toby; Daack-Hirsch, Sandra; Murray, Jeffrey C.; Marazita, Mary L.

doi:10.1002/ajmg.a.32295

Cited by 62 publications

(54 citation statements)

References 41 publications

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“…Our results for overall differences in dental anomalies between cases and control probands are also in line with most previous studies (Letra et al 2007;Vieira et al 2008b;Rawashdeh and Abu Sirdaneh 2009;Akcam et al 2010;Tannure et al 2012;Riis et al 2014). Despite the lack of radiographic access, which is challenging in an international sample, our estimates of the prevalence of dental anomalies are similar to studies based on radiographic images except for hypoplasia and supernumerary teeth.…”

Section: Discussionsupporting

confidence: 90%

Spectrum of Dental Phenotypes in Nonsyndromic Orofacial Clefting

et al. 2015

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Children with oral clefts show a wide range of dental anomalies, adding complexity to understanding the phenotypic spectrum of orofacial clefting. The evidence is mixed, however, on whether the prevalence of dental anomalies is elevated in unaffected relatives and is mostly based on small samples. In the largest international cohort to date of children with nonsyndromic clefts, their relatives, and controls, this study characterizes the spectrum of cleft-related dental anomalies and evaluates whether families with clefting have a significantly higher risk for such anomalies compared with the general population. A total of 3,811 individuals were included: 660 cases with clefts, 1,922 unaffected relatives, and 1,229 controls. Dental anomalies were identified from in-person dental exams or intraoral photographs, and case-control differences were tested using χ2 statistics. Cases had higher rates of dental anomalies in the maxillary arch than did controls for primary (21% vs. 4%, P = 3 × 10−8) and permanent dentitions (51% vs. 8%, P = 4 × 10−62) but not in the mandible. Dental anomalies were more prevalent in cleft lip with cleft palate than other cleft types. More anomalies were seen in the ipsilateral side of the cleft. Agenesis and tooth displacements were the most common dental anomalies found in case probands for primary and permanent dentitions. Compared with controls, unaffected siblings (10% vs. 2%, P = 0.003) and parents (13% vs. 7%, P = 0.001) showed a trend for increased anomalies of the maxillary permanent dentition. Yet, these differences were nonsignificant after multiple-testing correction, suggesting genetic heterogeneity in some families carrying susceptibility to both overt clefts and dental anomalies. Collectively, the findings suggest that most affected families do not have higher genetic risk for dental anomalies than the general population and that the higher prevalence of anomalies in cases is primarily a physical consequence of the cleft and surgical interventions.

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Section: Discussionsupporting

confidence: 90%

Spectrum of Dental Phenotypes in Nonsyndromic Orofacial Clefting

et al. 2015

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“…Recent evidence, however, suggests that individuals with clefts lie on a spectrum of overt phenotypes (CL, CLP, and CP) and a range of subclinical features, which may also be present in “unaffected” relatives of cases [Weinberg 2009]. These phenotypes include craniofacial measures [Weinberg et al, 2006], dental anomalies (tooth agenesis, microdontia, and supernumerary teeth) [Vieira et al, 2008], brain structural differences [Nopoulos et al, 2002; Weinberg et al, 2013], and dermatoglyphic lip print whorls [Neiswanger et al, 2009]. Subclinical phenotypes of the lip and palate include microform clefts (also known as congenital healed cleft lip), defects of the orbicularis oris muscle [Neiswanger, 2007; Rogers et al, 2008; Weinberg et al, 2008], bifid uvula, submucous cleft palate, and velopharyngeal insufficiency.…”

Section: Subclinical Phenotypes In Orofacial Cleft Familiesmentioning

confidence: 99%

Genetics of cleft lip and cleft palate

Leslie¹,

Marazita²

2013

American J of Med Genetics Pt C

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391

355

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Orofacial clefts are common birth defects and can occur as isolated, nonsyndromic events or as part of Mendelian syndromes. There is substantial phenotypic diversity in individuals with these birth defects and their family members: from subclinical phenotypes to associated syndromic features that is mirrored by the many genes that contribute to the etiology of these disorders. Identification of these genes and loci has been the result of decades of research using multiple genetic approaches. Significant progress has been made recently due to advances in sequencing and genotyping technologies, primarily through the use of whole exome sequencing and genome-wide association studies. Future progress will hinge on identifying functional variants, investigation of pathway and other interactions, and inclusion of phenotypic and ethnic diversity in studies.

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“…Following breakdown of the epithelium (Sun et al, 2000), a mesenchymal bridge forms, which then proliferates to form a continuous upper lip (Wang et al, 1995;Jiang et al, 2006). Since nonsyndromic cleft lip with or without cleft palate (CL/P) is the most common craniofacial birth defect (Jugessur and Murray, 2005), much effort has been focused on identifying some of the predisposing genetic alterations (Vieira et al, 2005(Vieira et al, , 2008. In addition, due to the complex interaction of genes and environment, it is necessary to use a variety of approaches and model organisms to understand the basis of this malformation.…”

Section: Introductionmentioning

confidence: 99%

The function and regulation of TBX22 in avian frontonasal morphogenesis

Higashihori¹,

Buchtová²,

Richman³

2010

Developmental Dynamics

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The frontonasal mass gives rise to the facial midline and fuses with the maxillary prominence to form the upper lip. Here we focus on the regulation and function of TBX22, a repressor dynamically expressed in the frontonasal mass. Both FGF and Noggin (a BMP antagonist) strongly induce gTBX22, however, each has opposite effects on morphogenesis -Noggin inhibits whereas FGF stimulates growth. To determine whether TBX22 mediates these effects, we used retroviruses to locally increase expression levels. RCAS::hTBX22 decreased proliferation, reduced expression of MSX2 and DLX5 and caused cleft lip. Decreased levels of endogenous gTBX22 were also observed but were not the primary cause of the phenotype as determined in rescue experiments. Our data suggest that genetic or environmental insults such as those affecting the BMP pathway could lead to a gain-of-function of TBX22 and predispose an individual to cleft lip. Developmental Dynamics 239:458-473,

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A genome wide linkage scan for cleft lip and palate and dental anomalies

Abstract: We revisited 46 families with two or more siblings affected with an orofacial cleft

Cited by 62 publications

References 41 publications

Spectrum of Dental Phenotypes in Nonsyndromic Orofacial Clefting

Spectrum of Dental Phenotypes in Nonsyndromic Orofacial Clefting

Genetics of cleft lip and cleft palate

The function and regulation of TBX22 in avian frontonasal morphogenesis

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