Genetic Factors in Nonsyndromic Orofacial Clefts

Khan, Mahamad Irfanulla; Cs, Prashanth; Srinath, N.

doi:10.1055/s-0041-1722951

Cited by 10 publications

(8 citation statements)

References 113 publications

(113 reference statements)

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“…Receptor-like tyrosine kinase ( RYK ) has been previously proposed as a cleft candidate gene [ 13 , 14 ]. RYK belongs to a group of conserved transmembrane molecules that have an extracellular domain that resemble the Wnt inhibitory factor (WIF) protein [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

PAX7, PAX9 and RYK Expression in Cleft Affected Tissue

2021

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Background and Objectives: Cleft lip with or without cleft palate is one of the most common types of congenital malformations. Transcription factors paired box 7 and 9 (PAX7, PAX9) and receptor-like tyrosine kinase (RYK) have been previously associated with the formation of orofacial clefts but their exact possible involvement and interactions in the tissue of specific cleft types remains uncertain. There is a limited number of morphological studies analyzing these specific factors in cleft affected tissue due to ethical aspects and the limited amount of available tissue material. This study analyses the presence of PAX7, PAX9, and RYK immunopositive structures within different cleft affected tissue to assess their possible involvement in cleft morphopathogenesis. Materials and Methods: Cleft affected tissue was collected from non-syndromic orofacial cleft patients during cleft correcting surgery (36 patients with unilateral cleft lip, 13 patients with bilateral cleft lip, 26 patients with isolated cleft palate). Control group oral cavity tissue was obtained from 7 patients without cleft lip and palate. To evaluate the number of immunopositive structures in the cleft affected tissue and the control group, a semiquantitative counting method was used. Non-parametric statistical methods (Kruskal–Wallis H test, Mann–Whitney U test, and Spearman’s rank correlation) were used. Results: Statistically significant differences for the number of PAX7, PAX9, and RYK-positive cells were notified between the controls and the patient groups. Multiple statistically significant correlations between the factors were found in each cleft affected tissue group. Conclusions: PAX7, PAX9, and RYK have a variable involvement and interaction in postnatal morphopathogenesis of orofacial clefts. PAX7 is more associated with the formation of unilateral cleft lip, while PAX9 relates more towards the isolated cleft palate. The stable presence of RYK in all cleft types indicates its possible participation in different facial cleft formations.

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Section: Introductionmentioning

confidence: 99%

PAX7, PAX9 and RYK Expression in Cleft Affected Tissue

2021

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“…Due to the fact that 99.6 to 99.9% of the human genome is shared by all people, consanguineous marriages have had a negligible effect on sequencing. 19 20 If two siblings gave birth, the child will have two grandparents rather than four. Under these circumstances, the child is more likely to inherit two copies of a harmful recessive gene (allele).…”

Section: Discussionmentioning

confidence: 99%

Analysis of Consanguinity as Risk Factor of Nonsyndromic Cleft Lips with or without Palate

Rochmah,

Harumsari,

Christiono

et al. 2023

Eur J Dent

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Objectives The etiologies of nonsyndromic cleft lips with or without palate (NS CL/P) are multifactorial, which include consanguineous marriages. The incidence of NS CL/P is relatively high in Indonesia notably in one of Indonesia's tribes whose members frequently marry close cousins. Thus, the purpose of this study is to analysis consanguinity as risk factor of NS CL/P in Sasak tribe, East Lombok, Indonesia Materials and Methods An observational analysis was made of a collected database of NS CL/P patients treated in social services in regency hospital of Dr. Soejono Selong, East Lombok, Indonesia. Demographic data such as age, gender, address (urban/rural), parent's education, presence or absence of consanguinity, type of clefts, and a three-generation pedigree were collected by interview and hospital medical record. Before analysis, patient information was anonymized and deidentified. From 2016 to 2018, each of 100 cleft and normal subjects with their Sasak parent were audited. The risk factors were analyzed statistically using odds ratio (OR) and chi-squared test. Results Consanguineous marriages identified 54 cases (54%), and 10 cases (10%) out of a total each 100 NS CL/P and controls, respectively. The majority of consanguinity (53.7%) was discovered in marriages between first cousins. NS CL/P cases were statistically linked (p = 0.00) with consanguineous marriages (OR: 10; 95% confidence interval: 1.6–3.1); in which the most prevalent case is unilateral cleft lips. Conclusion Consanguineous marriage increases the risk of NS CL/P in Sasak tribe, East Lombok, Indonesia. The development of strategies to educate communities on the impacts of culture-consanguineous marriage is required. The genetic inheritance from their ancestor may be responsible for the increased incidence of NS CL/P.

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“… 8 9 The highest prevalence rate is found in Asians and American Indians (1:500), the intermediate in Europeans (1:1,000), and the lowest in Africans (1:2,500). 10 In India, the incidence of clefts ranges between 1:800 and 1:1,000, with three infants born with some form of cleft every hour. 11 Consanguinity is a risk factor for nonsyndromic CL/P in the Indian population, according to a 13-year retrospective study from a cleft center.…”

Section: Introductionmentioning

confidence: 99%

Maternal Transmission of the PAX7 Single Nucleotide Polymorphisms among Indian Cleft Trios

Khan

Cs²,

Mustak

et al. 2023

Glob Med Genet

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Cleft lip and/or cleft palate (CL/P) is one of the most common congenital anomalies of the human face with a complex etiology involving multiple genetic and environmental factors. Several studies have shown the association of the paired box 7 (PAX7) gene with CL/P in different populations worldwide. However, the current literature reveals no reported case-parent trio studies to evaluate the association between the PAX7 gene and the risk of nonsyndromic cleft lip and/or palate (NSCL/P) in the Indian population. Hence, the purpose of this study was to assess the PAX7 gene single nucleotide polymorphisms (SNPs) in the etiology of NSCL/P among the Indian cleft trios. Forty Indian case-parent trios of NSCL/P were included. The cases and their parents' genomic DNA were extracted. The SNPs rs9439714, rs1339062, rs6695765, rs742071, and rs618941of the PAX7 gene were genotyped using the Agena Bio MassARRAY analysis. The allelic transmission disequilibrium test was performed using PLINK software while pair-wise linkage disequilibrium by the Haploview program. The SNP rs9439714 showed evidence of association (p-value = 0.02, odds ratio = 3) with NSCL/P. Considering the parent-of-origin effects, the SNPs rs9439714 and rs618941 showed an excess maternal transmission of allele C at rs9439714 (p-value = 0.05) and G allele at rs618941 (p-value = 0.04). The results of the present study suggested that the SNPs rs9439714 and rs618941 showed an excess maternal transmission of alleles suggestive of the possible role of the PAX7 gene involvement in the etiology of NSCL/P in the Indian population.

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Genetic Factors in Nonsyndromic Orofacial Clefts

Cited by 10 publications

References 113 publications

PAX7, PAX9 and RYK Expression in Cleft Affected Tissue

PAX7, PAX9 and RYK Expression in Cleft Affected Tissue

Analysis of Consanguinity as Risk Factor of Nonsyndromic Cleft Lips with or without Palate

Maternal Transmission of the PAX7 Single Nucleotide Polymorphisms among Indian Cleft Trios

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