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The dental abnormalities are the typical features of many ectodermal dysplasias along with congenital malformations of nails, skin, hair, and sweat glands. However, several reports of non-syndromic/isolated tooth agenesis have also been found in the literature. The characteristic features of hypohidrotic ectodermal dysplasia (HED) comprise of hypodontia/oligodontia, along with hypohidrosis/anhidrosis, and hypotrichosis. Pathogenic variants in EDA, EDAR, EDARADD, and TRAF6, cause the phenotypic expression of HED. Genetic alterations in EDA and WNT10A cause particularly non-syndromic/isolated oligodontia. In the current project, we recruited 57 patients of 17 genetic pedigrees (A-Q) from different geographic regions of the world, including Pakistan, Egypt, Saudi Arabia, and Syria. The molecular investigation of different syndromic and non-syndromic dental conditions, including hypodontia, oligodontia, generalized odontodysplasia, and dental crowding was carried out by using exome and Sanger sequencing. We have identified a novel missense variant (c.311G&gt, A, p.Arg104His) in WNT10A in three oligodontia patients of family A, two novel sequence variants (c.207delinsTT, p.Gly70Trpfs*25 and c.1300T&gt, G, p.Try434Gly) in EDAR in three patients of family B and four patients of family C, respectively. To better understand the structural and functional consequences of missense variants in WNT10A and EDAR on the stability of the proteins, we have performed extensive molecular dynamic (MD) simulations. We have also identified three previously reported pathogenic variants (c.1076T&gt, C, p.Met359Thr), (c.1133C&gt, T, p.Thr378Met) and (c.594_595insC, Gly201Argfs*39) in EDA in family D (four patients), E (two patients) and F (one patient), correspondingly. Presently, our data explain the genetic cause of 18 syndromic and non-syndromic tooth agenesis patients in six autosomal recessive and X-linked pedigrees (A-F), which expand the mutational spectrum of these unique clinical manifestations.

Mitochondrial disorders (MIDs) shows overlapping clinical presentations owing to the genetic and metabolic defects of mitochondria. However, specific relationship between inherited mutations in nuclear encoded mitochondrial proteins and their functional impacts in terms of metabolic defects in patients is not yet well explored. Therefore, using high throughput whole exome sequencing (WES), we screened a chronic kidney disease (CKD) and sensorineural hearing loss (SNHL) patient, and her family members to ascertain the mode of inheritance of the mutation, and healthy population controls to establish its rare frequency. The impact of mutation on biophysical characteristics of the protein was further studied by mapping it in 3D structure. Furthermore, LC-MS tandem mass spectrophotometry based untargeted metabolomic profiling was done to study the fluctuations in plasma metabolites relevant to disease causative mutations and kidney damage. We identified a very rare homozygous c.631G > A (p.Val211Met) pathogenic mutation in RMND1 gene in the proband, which is inherited in an autosomal recessive fashion. This gene is involved in the mitochondrial translational pathways and contribute in mitochondrial energy metabolism. The p.Val211Met mutation is found to disturb the structural orientation (RMSD is −2.95 Å) and stability (ΔΔG is −0.552 Kcal/mol) of the RMND1 protein. Plasma metabolomics analysis revealed the aberrant accumulation of metabolites connected to lipid and amino acid metabolism pathways. Of these metabolites, pathway networking has discovered ceramide, a metabolite of sphingolipids, which plays a role in different signaling cascades including mitochondrial membrane biosynthesis, is highly elevated in this patient. This study suggests that genetic defects in RMND1 gene alters the mitochondrial energy metabolism leading to the accumulation of ceramide, and subsequently promote dysregulated apoptosis and tissue necrosis in kidneys. Keywords: Chronic kidney disease, RMND1, Metabolomics, Sphingolipids, Ceramide

Oral-facial-digital syndromes are characterized by abnormalities in the oral cavity, face and digits. To date, 13 types with different modes of inheritance have been distinguished based on characte...

Background/aim: Congenital heart disease (CHD) is a common birth defect. Many studies have reported GATA4 mutations in patients with CHD, mainly septal defects. This study aimed to investigate the GATA4 exon 1 mutation in Egyptian patients with isolated congenital heart defects as a possible causative mutation. Materials and methods: Screening for mutations or any sequence variations in exon 1 of the GATA4 gene was carried out by PCR amplification followed by direct sequencings in 165 Egyptian patients with different nonsyndromic congenital heart diseases and 93 controls who were matched in terms of age and sex. Thorough clinical assessments were done for all subjects, along with X-ray, 2D echocardiography, and Doppler examinations. Results: The most common CHD among our cases was isolated ventricular septal defect (VSD) in 47.3% (78/165), followed by isolated atrial septal defect. A novel nonsynonymous sequence variation in fragment 2 (P193H) of exon 1 of GATA4 was detected in 15 (9.1%) of the subjects with septal defects. This mutation was not seen in any of the control group subjects. Conclusion: There is a high prevalence of exon 1 GATA4 mutation (9.1%) in our study compared to other studies in different populations, which may correlate with different ethnic populations.

Genetic factors in the form of maternal or fetal single gene disorders, chromosomal abnormalities, inherited thrombophilia and other genes involved are the main causes of recurrent abortion (RA). The risk of miscarriage is highest among couples where the woman is >35 years of age and the man >40 years of age. In about 50-70% of miscarriage, a chromosome abnormality is identified in the products of conception, this chromosomal abnormality derived from one parent or the recurrence of a numerical abnormality. In about 3-5% of couples with two or three spontaneous pregnancy losses, a balanced chromosome rearrangement was found in one member of the couple. Also man's factors have an important role in RA since the man gamete contributes one-half of the genomic content to the embryo. Moreover the paternally expressed genes may have an impact on implantation, placental proliferation, and placenta quality. So any situation which leads damage of sperms DNA (e.g. varicocele) will be associated with a reduction in some fertility indices.

This study was aimed at assessing the attitude of health care professionals in Jeddah city toward prenatal diagnosis (PND) and termination of pregnancy (TOP). A cross-sectional study was conducted, and the participants completed a self-administered questionnaire. Approximately 82% of participants showed a consistent trend of accepting PND when appropriate, and 47.5% of the respondents were in favor of TOP if the fetus had a severe disease. Compared with men (69.3%), a significantly greater number of women (88%) accepted to have PND. The most acceptable prenatal diagnostic tests in the study were invasive techniques as most of the participants thought that noninvasive tests were nonspecific.

We report a two years old Egyptian girl, the first birth of consanguineous marriage with clinical findings consistent with the diagnosis of the autosomal recessive multiple pterygium syndrome (Escobar) (growth retardation, craniofacial dysmorphism, multiple pterygia, kyphoscoliosis, multiple joint contractures especially affecting the lower limbs). What characterizes out patient was the extensive pterygia of the fingers which kept them permanently flexed, while they were very mild in the neck, axillary folds and knee joints. Our patient suffered also from mental retardation although mentality is commonly reported to be normal in this syndrome. MRI of the spine revealed widened spinal canal and engorged intraspinal vessels, which were not reported before. Keywords : Multiple pterygium syndrome; Joint contractures; Kyphoscoliosis; Autosomal recessive

Nutritional genetics is considered as the combination of nutrigenomics and nutrigenetics. Nutrigenomics is establishing the effects of ingested nutrients and other food components on gene expression and gene regulation. It will also determine the individual nutritional requirements based on the genetic makeup of the person (personalized diet) as well as the association between diet and chronic diseases which will help to understand the etiologic aspects of chronic diseases such as cancer, type-2 diabetes, obesity and cardiovascular disease (CVS). Nutrigenetics on the other hand identifies how the genetic makeup of a particular individual co-ordinates his or her response to various dietary nutrients. It also reveals why and how people respond differently to the same nutrient. The present review will focus upon interaction of genetic background and diet with regard to development of such life threatening chronic conditions as obesity, cardiovascular disease (CVD), and cancer that are responsible for the majority of deaths in developed Western countries.

Sjogren-Larsson syndrome (SLS) is a neurocutaneous disorder inherited in an autosomal recessive fashion. SLS patients are characterized by lipid metabolism error, primarily leading to cardinal signs of ichthyosis, spasticity and mental retardation. Additional signs include short stature, epilepsy, retinal abnormalities and photophobia. More than 90 mutations of the ALDH3A2 gene have been reported for SLS, and such variants can be successfully detected at a rate of 94% by direct DNA sequencing. We performed direct sequencing of ALDH3A2 gene from the index patient, however, no mutation could be detected. HumanCytoSNPs12 array analysis and subsequent targeted single nucleotide polymorphism analysis revealed a novel deletion mutation at chromosome 17p11.2. This 67-Kb region includes the first five coding exons of ALDH3A2, and is flanked by rs2245639 and rs962801. To the best of our knowledge, this mutation is novel and our findings broaden the mutation spectrum of ALDH3A2 causing SLS phenotype.