The development of craniofacial complex and dental structures is a complex and delicate process guided by specific genetic mechanisms. Genetic and environmental factors can influence the execution of these mechanisms and result in abnormalities. An insight into the mechanisms and genes involved in the development of orofacial and dental structures has gradually gained by pedigree analysis of families and twin studies as well as experimental studies on vertebrate models. The development of novel treatment techniques depends on in-depth knowledge of the various molecular or cellular processes and genes involved in the development of the orofacial complex. This review article focuses on the role of genes in the development of nonsyndromic orofacial, dentofacial variations, malocclusions, excluding cleft lip palate, and the advancements in the field of molecular genetics and its application to obtain better treatment outcomes.
Orofacial clefts (OFCs) are the most common congenital birth defects in humans and immediately recognized at birth. The etiology remains complex and poorly understood and seems to result from multiple genetic and environmental factors along with gene-environment interactions. It can be classified into syndromic (30%) and nonsyndromic (70%) clefts. Nonsyndromic OFCs include clefts without any additional physical or cognitive deficits. Recently, various genetic approaches, such as genome-wide association studies (GWAS), candidate gene association studies, and linkage analysis, have identified multiple genes involved in the etiology of OFCs.
This article provides an insight into the multiple genes involved in the etiology of OFCs. Identification of specific genetic causes of clefts helps in a better understanding of the molecular pathogenesis of OFC. In the near future, it helps to provide a more accurate diagnosis, genetic counseling, personalized medicine for better clinical care, and prevention of OFCs.
Ehlers-Danlos syndrome (EDS) is a group of clinically and genetically heterogeneous disorder of soft connective tissues. The hallmark clinical features of the EDS are hyperextensible skin, hypermobile joints, and fragile vessels. It exhibits associated symptoms including contractures of muscles, kyphoscoliosis, spondylodysplasia, dermatosparaxis, periodontitis, and arthrochalasia. The aim of this study is to determine the exact subtype of EDS by molecular genetic testing in a family segregating EDS in an autosomal recessive manner. Herein, we describe a family with two individuals afflicted with EDS. Whole exome sequencing identified a homozygous missense mutation (c.2050G > A; p.Glu684Lys) in the COL1A1 gene in both affected individuals, although heterozygous variants in the COL1A1 are known to cause EDS. Recently, only one report showed homozygous variant as an underlying cause of the EDS in two Saudi families. This is the second report of a homozygous variant in the COL1A1 gene in a family of Saudi origin. Heterozygous carriers of COL1A1 variant are asymptomatic. Interestingly, the homozygous variant identified previously and the one identified in this study are same (c.2050G > A). The identification of a unique homozygous mutation (c.2050G > A) in three Saudi families argues in favor of a founder effect.
Cerebrovascular accidents (CVAs) are vascular multifactorial, multigenic ailments with intricate genetic, environmental risk influences. The present study aimed to establish affiliation of CVAs/stroke with blood parameters, differences in prescribed drugs consumption, and with differences in homocysteine pathway genes polymorphisms. The participants in study included controls n = 251, transient ischemic attack (TIA) patients n = 16, and stroke cases n = 122, respectively, (total participants, n = 389). The analyzed single nucleotide polymorphisms (SNPs) included C677T(rs1801133), A1298C(rs1801131) of methylene tetrahydrofolate reductase (MTHFR), A2756G(rs1805087) of methyl tetrahydrofolate homocysteine methyltransferase/methionine synthase (MS), and the A192G(rs662) of paraoxonase 1(PON1) genes, all validated by tetra-primer allele refractory mutation system polymerase chain reaction (T-ARMS-PCR). The insertion deletion (I/D; rs4646994) polymorphism in angiotensin converting enzyme (ACE) gene was analyzed using routine PCR. All studied traits were scrutinized through analysis of variance (ANOVA), and later through regression analysis. Through ANOVA and multiple comparison, there was association of CVA with serum homocysteine, cholesterol, and with diastolic blood pressure readings. When data was subjected to regression, serum homocysteine and diastolic blood pressure (significant through ANOVA), as well as two additional traits, high-density lipoproteins (HDL), and rs1801133 MTHFR SNP sustained statistical significance and noteworthy odds in relation to CVA and stroke. The ailments affecting cerebral vasculature are mutifactorial, whereby genes, proteins, and environmental cues all exert cumulative effects enhancing CVA risk. The current study emphasizes that SNPs and variation in circulating biomarkers can be used for screening purposes and for reviewing their effects in stroke/CVA-linked risk progression.
Background DNA repair systems play an important role in maintaining the integrity of the human genome. Deficiency in the repair capacity due to either mutations or inherited polymorphisms in DNA repair genes may contribute to variations in the DNA repair capacity and subsequently susceptibility to cancer.
Objectives This study aimed to investigate the association between Excision repair cross-complementation groups 2 (ERCC2) single nucleotide polymorphisms (SNPs rs1799793 and rs13181) and the response to platinum-based chemotherapy among patients with oral squamous cell carcinoma (OSCC).
Methodology Polymerase chain reaction‐based restriction fragment length polymorphism analysis was used to determine the polymorphism from a total of 150 OSCC patients and 150 normal tissues of same patients were collected as controls for this study.
Results ERCC2 GA (Asp312Asn) AC (Lys751Gln) genotypes were significantly associated (p = 0.0001 and p = 0.0004, respectively) with OSCC patients, when compared with the controls. These findings suggest that potentially functional SNPs in ERCC2 may contribute to OSCC risk. This study highlights the genetic variant that might play a role in mediating susceptibility to OSCC in this population. An understanding of DNA repair gene polymorphisms might not only enable risk assessment, but also response to therapy, which target the DNA repair pathway.
Purpose Turner syndrome is a sex chromosomal aberration where majority of the patients have 45,X karyotype, while several patients are mosaic involving 45,X/46,XX; 46,X,i(Xq); and other variants. Cytogenetic analysis, karyotyping, is considered to be the “gold standard” to detect numerical and structural chromosomal abnormalities. In the recent years, alternative approaches, such as array comparative genomic hybridization (aCGH), have been widely used in genetic analysis to detect numerical abnormalities as well as unbalanced structural rearrangements. In this study, we report the use of karyotyping as well as aCGH in detecting a possible Turner syndrome variant.
Methods An apparent 16-year-old female was clinically diagnosed as Turner syndrome with premature ovarian failure and short stature. The genetic diagnosis was performed for the patient and the parents by karyotyping analysis. aCGH was also performed for the patient.
Main Findings Cytogenetic analysis of the patient was performed showing variant Turner syndrome (46,X,i(X)(q10)[26]/46,X,del(X)(q11.2)[11]/45,X[8]/46,XX[5]). The patient's aCGH result revealed that she has a deletion of 57,252kb of Xp22.33-p11.21 region; arr[GRCh37] Xp22.33-p11.21 (310,932-57,563-078)X1. Both aCGH and fluorescence in situ hybridization (FISH) results suggested that short stature Homeobox-containing (SHOX) gene, which is located on Xp22.33, was deleted, though FISH result indicated that this was in a mosaic pattern.
Conclusion In the recent years, aCGH has become the preferred method in detecting numerical abnormalities and unbalanced chromosomal rearrangements. However, its use is hindered by its failure of detecting mosaicism, especially low-level partial mosaicism. Therefore, although the resolution of the aCGH is higher, the cytogenetic investigation is still the first in line to detect mosaicism.