موقف الاصولیین من افعال النبیینﷺ

The Prophet (s. a. w.) was after all a human being with perfect human nature; whatever he did in his daily life represented human nature. All of his unanimously authentic doings have been classified by legal theorists into two major categories, the doings allowed to the Prophet (s. a. w.) alone with the exclusion of his followers and the doings that were meant to explain particular apparently ambiguous sayings. The latter category is further divided into two other categories: ( I) those acts of the Holy Prophet which explicitly refer to its explanatory nature, and (r) those acts whose explanatory nature is confirmed by other source. Islamic legal theorists have unanimity over the legal status of all categories of the Prophet’s (s. a. w.) acts. Certain acts of the Prophet (s. a. w.) are mandatoryfor him but non-mandatory for his followers; certain other acts are lawful for the Prophet (s. a. w.) but unlawful for believers; some acts are obligatory for the believers; and some acts of the Prophet (s. a. w.) are mere supererogatory. There are some acts of the Prophet (s. a. w.) on which legal theorists have not said anything concerning their legal status. The present paper represents an analysis of the views of legal theorists about the acts ofthe Prophet (s. a. w.) .

Molecular Basis of Autosomal Recessive Intellectual Disability in Pakistani Population

Intellectual disability (ID) is a lifelong condition with tremendous clinical and genetic heterogeneity, affecting 1-3% population worldwide. It is characterized by cognitive impairment as well as adaptive deficits originating before the age of 18 years. Severity of ID along with associated clinical manifestation, determines the need of support in affected individuals. Genetics and environment both equally contribute to its etiology. During last few years, successive large scale studies using next generation sequencing (NGS) technologies have added many new genes to the existing gene repertoire for ID. Carrying out research studies in the inbred populations will allow the identification of recessive genetic defects. Therefore present project was designed to elucidate the molecular basis of autosomal recessive intellectual disability (ARID) in Pakistani population which shows high consanguinity with estimates more than 50%. So as to achieve the objectives, eighty families with history of intellectual disability were recruited from different cities. Complete medical history, written informed consents and blood samples were collected from the participating individuals. Forty nine families were selected on the basis of pedigree structures and processed further for genetic characterization through linkage analysis, whole exome sequencing (WES) and Sanger sequencing. Linkage analysis was carried out to screen thirty seven families for the presence of reported ID loci. Two families PKMR288 and PKMR304 showed homozygous regions linked with known ARID loci MRT10/ MRT20 and MRT1 respectively. Mapping of known X chromosome loci revealed linkages in six ID families PKMR229, PKMR244, PKMR251, PKMR253, PKMR271 and PKMR297. Whole exome sequencing (WES) was performed on twelve selected families. After exome data analysis and variant prioritization, pathogenic variants were identified in seven families. A reported frameshift mutation in ASPM gene was segregating in PKMR62 whereas a novel missense mutation in known THOC6 gene was detected in PKMR427. Potentially novel candidate ARID genes containing missense mutations were found in four families: EHBP1L1 in PKMR198, AREL1 in PKMR258, TM2D3 in PKMR325 and PRKAR2B in PKMR326. There was one family PKMR425 with missense mutation identified in FOXO4, a novel candidate gene for X-linked ID. Sanger sequencing was used to confirm these mutations and subsequently their co-segregation with ID phenotype in respective families. Mutation detection by means of high-throughput exome sequencing proved itself to be a cost-effective and time-saving approach. All the novel candidate genes were found to be implicated in different biological pathways related directly or indirectly to the brain growth and activity through in silico analysis. These findings will expand the existing database for genes involved in ARID, and will provide new insights into the molecular mechanisms of neurodevelopment leading to advancements in cognitive diagnostics and therapeutics.