قدیم پنجابی زبان: ہڑپا وادی دی زبان

There are different theories about languages in the world. Linguistics provided different views on the origin of different languages. The Punjabi language is a one of the oldest languages in the world. According to my view, its origin is Dakan, Punjab, Sind etc. This article explores the effects of the Harappan Era on the Punjabi language. Historical references have been made to prove that the language of Harappa was ancient Punjabi.

Molecular Characterization of Familial Epilepsies

Epilepsy is an ailment of central nervous system that is characterized by inherent tendency of the brain to produce unprovoked seizures. Epilepsy could be idiopathic i.e.without a known cause (also cryptogenic) or symptomatic i.e. with a discernable clinical cause. Genetics play a crucial role in pathogenesis of both idiopathic and symptomatic epilepsies and molecular characterization holds prime importance and significance to delimit the genetic causes of the ailment. In the current study, five families (designated here as EP-01, EP-02, EP-03, EP-10 and EP-22) affected with idiopathic epilepsies were ascertained at molecular level through whole exome sequencing and Sanger sequencing to identify underlying genetic variants. The families EP-01 and EP-22 were affected with autosomal recessive progressive myoclonic epilepsy (also called Lafora disease). In family EP-01, we identified a novel missense variant c.262T>G in the EPM2A gene segregating with the disease phenotype. In silico analyses supported deleterious effects of the mutation by affecting the carbohydrate binding module of the EPM2A translated protein. In family EP-22, a recurrent nonsense variant c.793C>T in the NHLRC1 gene was identified as the likely cause of the disease phenotype in the family. The family EP-03 was affected with a Dravet-like phenotype. Whole exome sequencing identified a novel missense variant c.1342C>T in GRAMD1A gene. The variant was found segregating within the family in autosomal recessive mode and In silico analyses predicted deleterious effects of this variant on the protein function. Therefore, we suggest this novel GRAMD1A variant c.1342C>T identified in the current study as the likely cause of the epilepsy phenotype in the family EP-03. The involvement of GRAMD1A in epilepsy might be through involvement of endoplasmic reticulum - plasma membrane (ER-PM) transportation pathway. However, functional studies are required to explore the mechanism of pathogenesis. Families EP-02 and EP-10 were affected with autosomal dominant focal epilepsies. The family EP-02 presented with familial focal epilepsy with variable foci and the family EP-10 with lateral temporal lobe epilepsy. Both families were subjected to whole exome sequencing and the data were analyzed to find potential candidate variants that were tested for segregation in the affected families through Sanger sequencing. However, causative genetic variants were not identified in these families. Utilizing the standard Sanger sequencing and next generation sequencing technology (whole exome sequencing), we were able to find the likely cause of the disease in three Pakistani families affected with different epileptic pathologies at molecular level. These included a novel missense EPM2A variant, a recurrent nonsense NHLRC1 variant and a novel missense GRAMD1A variant. Two affected families were not resolved and warrant whole genome sequencing to unravel the genetic cause underlying epilepsy phenotype in these families. These data should be helpful in molecular diagnosis and screening of carriers in the affected families.