Identification of Copy Number Variation Among Nonsyndromic Cleft Lip and or Without Cleft Palate With Hypodontia: A Genome-Wide Association Study

Ghazali, Norliana; Rahman, Normastura Abd; Azlina, Ahmad; Sulong, Sarina; Kannan, Thirumulu Ponnuraj

doi:10.3389/fphys.2021.637306

Cited by 5 publications

(3 citation statements)

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“…This clinical association could be the phenotype of cleft palate lateral synechiae syndrome (CPLS or cleft palate and congenital alveolar synechia syndrome) [ 7 , 12 ], orofaciodigital syndromes (OFD), Fryns syndrome [ 15 ] and IRF6-related disorders or other syndromes interacting with IRF6 in a reciprocal complex network [ 16 ]. Actually, it is debated if the first genetic approach should be a direct Sanger sequencing of only IRF6 , a panel gene study of more genes, and/or an aCGH [ 7 , 17 ]. Indeed, overlapping features, sometimes including neonatal hypoglycemia, warrant a more general investigation, since there are other genes of interest in the differential diagnosis of IRF6-related disorders.…”

Section: Discussionmentioning

confidence: 99%

Novel de novo missense mutation in the interferon regulatory factor 6 gene in an Italian infant with IRF6-related disorder

Schierz¹,

Amoroso

Antona³

et al. 2022

Ital J Pediatr

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Background Congenital maxillomandibular syngnathia is a rare craniofacial anomaly leading to difficulties in feeding, breathing and ability to thrive. The fusion may consist of soft tissue union (synechiae) to hard tissue union. Isolated cases of maxillomandibular fusion are extremely rare, it is most often syndromic in etiology. Case presentation Clinical management of a female newborn with oromaxillofacial abnormities (synechiae, cleft palate, craniofacial dysmorphisms, dental anomaly) and extraoral malformations (skinfold overlying the nails of both halluces, syndactyly, abnormal external genitalia) is presented. The associated malformations addressed to molecular genetic investigations revealing an interferon regulatory factor 6 (IRF6)-related disorder (van der Woude syndrome/popliteal pterygium syndrome). A novel de novo heterozygous mutation in exon 4 of IRF6 gene on chromosome 1q32.2, precisely c.262A > G (p.Asn88Asp), was found. Similarities are discussed with known asparagine missense mutations in the same codon, which may alter IRF6 gene function by reduced DNA-binding ability. A concomitant maternal Xp11.22 duplication involving two microRNA genes could contribute to possible epigenetic effects. Conclusions Our reported case carrying a novel mutation can contribute to expand understandings of molecular mechanisms underlying synechiae and orofacial clefting and to correct diagnosing of incomplete or overlapping features in IRF6-related disorders. Additional multidisciplinary evaluations to establish the phenotypical extent of the IRF6-related disorder and to address family counseling should not only be focused on the surgical corrections of syngnathia and cleft palate, but also involve comprehensive otolaryngologic, audiologic, logopedic, dental, orthopedic, urological and psychological evaluations.

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Section: Discussionmentioning

confidence: 99%

Novel de novo missense mutation in the interferon regulatory factor 6 gene in an Italian infant with IRF6-related disorder

Schierz¹,

Amoroso

Antona³

et al. 2022

Ital J Pediatr

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“…However, those who had undergone orthodontic treatment were excluded from the study. This study has a sample population and design similar to those of the previous study [ 23 ]. The sample size for genetic abnormalities was calculated using the single proportion formula based on the prevalence of genetic aberrations [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

Identification of copy neutral loss of heterozygosity on chromosomes 1p, 1q, and 6p among nonsyndromic cleft lip and/or without cleft palate with hypodontia

Ghazali,

Rahman,

Kannan

et al. 2023

BMC Oral Health

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Background Nonsyndromic cleft lip and/or without cleft palate (NSCL/P) with or without hypodontia is a common developmental aberration in humans and animals. This study aimed to identify the loss of heterozygosity (LOH) involved in hypodontia and NSCL/P pathogenesis. Methods This is a cross-sectional study that conducted genome-wide copy number analysis using CytoScan 750K array on salivary samples from Malay subjects with NSCL/P with or without hypodontia aged 7–13 years. To confirm the significant results, simple logistic regression was employed to conduct statistical data analysis using SPSS software. Results The results indicated the most common recurrent copy neutral LOH (cnLOH) observed at 1p33-1p32.3, 1q32.2-1q42.13 and 6p12.1-6p11.1 loci in 8 (13%), 4 (7%), and 3 (5%) of the NSCL/P subjects, respectively. The cnLOHs at 1p33-1p32.3 (D1S197), 1q32.2-1q42.13 (D1S160), and 6p12.1-6p11.1 (D1S1661) were identified observed in NSCL/P and noncleft children using microsatellite analysis markers as a validation analysis. The regions affected by the cnLOHs at 1p33-1p32.3, 1q32.2-1q42.13, and 6p12.1-6p11.1 loci contained selected genes, namely FAF1, WNT3A and BMP5, respectively. There was a significant association between the D1S197 (1p33-32.3) markers containing the FAF1 gene among NSCL/P subjects with or without hypodontia compared with the noncleft subjects (p-value = 0.023). Conclusion The results supported the finding that the genetic aberration on 1p33-32.3 significantly contributed to the development of NSCL/P with or without hypodontia. These results have an exciting prospect in the promising field of individualized preventive oral health care.

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“…This is considered a scan for “modifiers” because it can detect loci where the effects are different between the case groups (but has higher power for opposite effects) and has no power to detect loci important for both case groups. This approach has been used to contrast CL and CLP (Carlson et al, 2017), laterality (Curtis, Chang, Lee, et al, 2021) and sidedness differences in CL/P (Curtis, Chang, Sun, et al, 2021), and to contrast OFC cases with and without hypodontia (Ghazali et al, 2021).…”

Section: Genome‐wide Studies Of Ofcsmentioning

confidence: 99%

Genetic models and approaches to study orofacial clefts

Leslie

2022

Oral Diseases

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Introduction: Orofacial clefts (OFCs) are common craniofacial birth defects with heterogeneous phenotype and etiology. Geneticists have applied nearly every available method and technology for further understanding of the genetic architectures of OFCs.Objective: This review describes the evidence for a genetic etiology in OFCs, statistical genetic approaches employed to identify genetic causes, and how the results have shaped our current understanding of the genetic architectures of syndromic and nonsyndromic OFCs. Conclusion:There has been rapid progress toward elucidating the genetic architectures of OFCs due to the availability of large collections of DNA samples from cases, controls, and families with OFCs and the consistent adoption of new methodologies and novel statistical approaches as they are developed. Genetic studies have identified rare and common variants influencing risk of OFCs in both Mendelian and complex forms of OFCs, blurring the distinction traditional categories used in genetic studies and clinical medicine.

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Identification of Copy Number Variation Among Nonsyndromic Cleft Lip and or Without Cleft Palate With Hypodontia: A Genome-Wide Association Study

Cited by 5 publications

References 58 publications

Novel de novo missense mutation in the interferon regulatory factor 6 gene in an Italian infant with IRF6-related disorder

Novel de novo missense mutation in the interferon regulatory factor 6 gene in an Italian infant with IRF6-related disorder

Identification of copy neutral loss of heterozygosity on chromosomes 1p, 1q, and 6p among nonsyndromic cleft lip and/or without cleft palate with hypodontia

Genetic models and approaches to study orofacial clefts

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