Search

Polycystic ovary syndrome (PCOS) is a polygenic, endocrine disorder causing ovarian dysfunction. This syndrome encompasses a broad spectrum of phenotypic expression due to heterogeneity. This study aimed to investigate the prevalence and phenotypic factors contributing to the onset of PCOS in Pakistani women. Participating females (n=130) were recruited from different regions of Pakistan explicitly those who were trying to conceive for years. We designed a questionnaire having different subsections comprising questions related to psychological and environmental aspects linked with PCOS. We also analyzed the proportion of women having prior awareness about the genetic basis of the disease. The retrieved data was analyzed through SPSS V.21 by employing descriptive statistics. A Chi-square test was used to establish a correlation between PCOS and associated symptoms. Our findings suggest that factors like obesity, facial and abdomen hair growth, irregular periods, menstrual flow, cramps, and hormonal acne corresponds to PCOS in participating females with a p-value (0.000 < 0.05). Around half of the participants were reported to be experiencing one or other symptom related to PCOS from which hirsutism and anxiety were the most common. Furthermore, our findings indicate that multiple psychological and environmental factors contribute to the onset of the disease with a P-Value (0.000 < 0.05). However, a significantly higher p-value (0.247 > 0.05) for excessive hair loss in participants were observed demonstrating that hair loss is not linked with PCOS. In this survey, 46.5 % of participants responded that they know that PCOS can be inherited. 28.5 % of women responded that they had a family history of PCOS. Adopting a healthy lifestyle and maintaining a healthy weight can minimize the severity of PCOS. This survey evaluates different hypotheses which would facilitate a better understanding of the prevalence and associated symptoms of PCOS in Pakistan thereby enabling researchers to develop better diagnostic, management, and treatment strategies for patients.

Cockayne syndrome (CS) is a rare neurodegenerative disorder characterized by impaired neurological functions, cachectic dwarfism, microcephaly and photosensitivity. Complementation assays identify two groups of this disorder, CS type I (CSA) and CS type II (CSB), caused by mutations in ERCC8 and ERCC6, respectively.This study aimed to investigate the genetic basis of a consanguineous Pakistani family with three affected individuals presenting with typical clinical symptoms of CS.We employed whole exome sequencing of the proband and then Sanger sequenced all the family members to confirm its segregation in the family. Different bioinformatics tools were used to predict pathogenicity of this variant.Variants were filtered according to the pedigree structure. We identified a novel homozygous variant (c.202AT; p.Ile68Phe) in ERCC8 gene in the proband. The variant was found to segregate in the family.These findings add to the genetic heterogeneity of ERCC8 and expands the mutation spectrum. Also, identification of this variant can facilitate prenatal diagnosis/genetic counselling set ups in Pakistan where this disease largely remains undiagnosed.

Postpartum depression is a psychological condition that deteriorates a mother’s cognitive health and overall family functioning. This survey-based cross-sectional study was done on postpartum mothers between 15-40 years of age to determine the epidemiology of postpartum depression in Pakistan. Edinburg postnatal depression scale (EPDS) and an adapted relationship assessment tool were used to determine the prevalence of postpartum depression. A total of n=103 responses were collected from different regions of Pakistan. Univariate and Bivariate analyses, Pearson Correlation Tests, and Binary Logistic Regression Analyses were applied to investigate the predictors. Postpartum depression was found in 67.96 % of the participating women and EPDS was found to be the most reliable tool to evaluate postpartum depression.

In this chapter, we have focused on the journey of sorting genes and the connotation of genetic counseling started. In a literal sense, we will understand how genetic counseling could contribute to identifying pathogenicity and penetrance of genetic mutation/s in high-risk individual/s or populations. Great strides have been achieved in terms of diagnosis, management, and treatment of various genetic disorders due to rapid advancements in genetic research. The national Thalassemia Prevention Program of Cyprus has been one of the earliest and most celebrated successes in lowering the disease burden and improving life quality and survival rate in patients. The knowledge regarding gene/s and variant/s is quite instrumental for making important reproductive decisions and therapeutic interventions for both rare and common disorders. We also touch upon the associated ethical issues and challenges.

Current study was performed to evaluate the antioxidant and pharmacological potential of numerous common fruits. Prunus Domestica (Prunes) are excellent sources of dietary antioxidants and cause lowering of LDL cholesterol plasma level. Strawberries (Fragaria Ananassa) have ascorbic acid content (5-50 mg/100 g of fresh weight) and are effective in in oral cancer and cardiovascular diseases. Citrus fruits (Citrus limon) are rich in flavonoids (naringin and hesperidin), polyphenols and vitamin C; the extracts of citrus peels are effective against food borne bacteria. Lime oil from Citrus aurantifolia has been used as a component of skin care products and to impart tase and flavor in food industry. Grapes (Vitis Vinifera) are rich in phenolic compounds and are active against cancer, cholera, smallpox, nausea, eye infections and skin/kidney/liver diseases. Blackberry (Rubus ulmifolius) contains polyphenol ingredients and possesses neuroprotection potential against age-related diseases. Different parts of Jamun or Java Plum (Syzygium Cumini) demonstrate excellent antioxidant and antimicrobial potential and used as a remedy for diabetes mellitus, leucorrhea, fever, constipation and gastropathy. Ziziphus mauritiana (Ber) consists of cyclopeptide alkaloid, lupine and ceanathone triterpenes; it displays sedatives, analgesic, antibacterial and excellent antioxidant potential. Vaccinium oxycoccus (cranberries) has 10mg/100g of ascorbic acid content; its extract can prevent urinary tract infections.

GPR56 gene is best known for its pivotal role in cerebral cortical development. Mutations in GPR56 give rise to cobblestone-like brain malformation, white matter changes and cerebellar dysplasia. This study aimed to identify causative variant in a consanguineous family having five individuals affected with developmental delay, mild to severe intellectual disability, speech impairment, strabismus and seizures. Whole exome sequencing was performed to identify mutation in affected individuals. Variants were filtered and further validated by Sanger sequencing and segregation analysis. A novel frameshift variant c.1601dupT leading to p.Ala535GlyfsTer17) was identified in GPR56 gene by whole exome sequencing and subsequent filtering. All five affected individuals were homozygous for the mutant allele while four asymptomatic individuals carried the variant in heterozygous state. Radiological findings of a representative patient presented features of GPR56-associated cobblestone like brain malformation. MRI findings suggested paucity of sulci, dilated ventricular system and brainstem atrophy. The microgyria were observed in a simplified gyral pattern (cobblestone). This single bp insertion, and the consequent frameshift, results in the truncation of GPR56 protein. This could result in a malformed cortex giving the brain a cobblestone like shape. Our study identified a 7th novel frameshift variant from Pakistani population in GPR56 gene, thus broadening mutation spectrum.

Hereditary Spastic paraplegias (HSPs) are heterogeneous group of degenerative disorders characterized by progressive weakness and spasticity of the lower limbs, combined with additional neurological features. This study aimed to identify causative gene variants in two nonrelated consanguineous Pakistani families segregating HSP. Whole exome sequencing (WES) was performed on a total of five individuals from two families including four affected and one phenotypically normal individual. The variants were validated by Sanger sequencing and segregation analysis. In family A, a novel homozygous variant c.604G > A (p.Glu202Lys) was identified in the CYP2U1 gene with clinical symptoms of SPG56 in 3 siblings. Whereas, a previously reported variant c.5769delT (p.Ser1923Argfs*28) in the SPG11 gene was identified in family B manifesting clinical features of SPG11 in 3 affected individuals. Our combined findings add to the clinical and genetic variability associated with CYP2U1 and SPG11 variants highlighting the complexity of HSPs. These findings further emphasize the usefulness of WES as a powerful diagnostic tool.

Spinocerebellar ataxias (SCA) comprise a heterogeneous group of inherited neurological disorders characterized by a range of symptoms from both cerebellar and extra cerebellar structures. We investigated the cause of autosomal recessive, congenital SCA in six affected family members from a large consanguineous family. Using whole-exome sequencing, we identified a homozygous ITPR1 missense variant [c.5360T>C; p.(L1787P)] segregating in all affected individuals. Heterozygous carriers were asymptomatic despite cerebellar hypoplasia. Variants in the ITPTR1 gene have previously been associated exclusively with autosomal dominant SCA15 and SCA29 with slow or no progression. The L1787 residue is highly conserved and the leucine to proline substitution has a predicted destabilizing effect on the protein structure. Additionally, the L1787P variant is located in a domain separated from previously described and dominant-acting missense variants consistent with a distinct effect on IP3R1 tetramer structure and function. Taken together, we show for the first time that a biallelic ITPR1 missense variant may cause an autosomal recessive and infantile onset SCA29, albeit with subclinical cerebellar hypoplasia in carriers. Our findings add to the genetic complexity of SCA29 and broaden the correlations between ITPR1 variants and their clinical expression.