Clinical and genetic investigation of 14 families with various forms of short stature syndromes.

Skeletal dysplasias are a heterogeneous group of disorders presenting mild to lethal defects. Several factors, such as genetic, prenatal, and postnatal environmental may contribute to reduced growth. Fourteen families of Pakistani origin, presenting the syndromic form of short stature either in the autosomal recessive or autosomal dominant manner were clinically and genetically investigated to uncover the underlying genetic etiology.

Satisfaction of patients in government medical teaching institutes of Peshawar Khyber Pakhtunkhwa, Pakistan: a cross-sectional analytical study.

Objective: To evaluate patient satisfaction and its associated factors in teaching hospitals.

Methods: The cross-sectional, analytical study was conducted from September to December 2022 at three publicsector medical teaching hospitals in Peshawar, Pakistan, and comprised adult patients of either admitted to various hospital wards for at least 2 days. Data was collected using a predesigned a closed-ended questionnaire assessing patient satisfaction in different domains like, facilitation at the admission, professional knowledge and skills of the attending doctors, quality of diagnostic and nursing services, and basic amenities.

The potential toxicity of chemically fabricated silver nanomaterials based on accumulation and histological changes in fish (Cyprinus carpio).

The bio-reductive fabrication of nanomaterials is a developing arena of study that seeks to fabricate nanoparticles (NPs) using microorganisms, plants, and animal blood. However, the chemical approach of AgNPs fulfills the need of abundant need of NPs. In contrast, chemically fabricated AgNPs are more toxic than biological AgNPs.

Exploring the natural products chemical space to abrogate the F3L-dsRNA interface of monkeypox virus to enhance the immune responses using molecular screening and free energy calculations.

Amid the ongoing monkeypox outbreak, there is an urgent need for the rapid development of effective therapeutic interventions capable of countering the immune evasion mechanisms employed by the monkeypox virus (MPXV). The evasion strategy involves the binding of the F3L protein to dsRNA, resulting in diminished interferon (IFN) production. Consequently, our current research focuses on utilizing virtual drug screening techniques to target the RNA binding domain of the F3L protein.

Nonsense variant in a consanguineous family expands the phenotype of KPTN gene-related syndrome to include hearing impairment.

A short report with two affected siblings from consanguineous family born with intellectual disability, motor disability, language deficit, and hearing impairment and found to carry biallelic nonsense variant in KPTN gene known to be associated with KPTN gene related syndrome.

A novel homozygous missense substitution p.Thr313Ile in the PDE6B gene underlies autosomal recessive retinitis pigmentosa in a consanguineous Pakistani family.

Background: Retinitis pigmentosa (RP) is one of the most frequent hereditary retinal diseases that often starts with night blindness and eventually leads to legal blindness. Our study aimed to identify the underlying genetic cause of autosomal recessive retinitis pigmentosa (arRP) in a consanguineous Pakistani family.

Methods: Following a detailed ophthalmological examination of the patients by an ophthalmologist, whole-exome sequencing was performed on the proband's DNA to delineate the genetic cause of RP in the family.

Biallelic mutations in FLG, TGM1, and STS genes segregated with different types of ichthyoses in eight families of Pakistani origin.

Background: Congenital ichthyosis is a diverse group of keratinization disorders associated with generalized scaling of skin of varying severity. The non-syndromic forms of congenital ichthyosis are further grouped into common ichthyosis (ichthyosis vulgaris and X-linked ichthyosis), autosomal recessive congenital ichthyosis, and keratopathic ichthyosis.

Objective: To identify sequence variants involved in different forms of hereditary ichthyoses.

Syntaxin 4 is essential for hearing in human and zebrafish.

Congenital hearing impairment (HI) is a genetically highly heterogeneous disorder in which prompt recognition and intervention are crucial to optimize outcomes. In this study, we used exome sequencing to investigate a large consanguineous Pakistani family with eight affected individuals showing bilateral severe-to-profound HI. This identified a homozygous splice region variant in STX4 (c.

A novel homozygous missense variant p.D339N in the PKLR gene correlates with pyruvate kinase deficiency in a Pakistani family: a case report.

Background: Pyruvate kinase deficiency is an exceptionally rare autosomal recessive Mendelian disorder caused by bi-allelic pathogenic variants in the PKLR gene. It is mainly characterized by chronic nonspherocytic hemolytic anemia though other symptoms such as splenomegaly, hepatomegaly, pallor, fatigue, iron overload, shortness of breath, hyperbilirubinemia, and gallstones might also prevail.

Case Presentation: We present here a novel genetic defect in the PKLR gene that correlates with pyruvate kinase deficiency phenotype in a consanguineous family from North-Western Pakistan.

Novel splicing-site mutation in DCAF17 gene causing Woodhouse-Sakati syndrome in a large consanguineous family.

Background: Woodhouse-Sakati syndrome is a rare autosomal recessive disease with endocrine and neuroectodermal aberrations with heterogeneous phenotypes and disease course. The most common phenotypes of the disease are progressive sensorineural hearing loss and alopecia, mild-to-moderate mental retardation and hypogonadism. The disease results from mutations in the DCAF17 gene.

Cobalt Single Atom Incorporated in Ruthenium Oxide Sphere: A Robust Bifunctional Electrocatalyst for HER and OER.

The development of highly active and stable bifunctional noble-metal-based electrocatalysts for the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) is a crucial goal for clean and renewable energy, which still remains challenging. Herein, we report an efficient and stable catalyst comprising a Co single atom incorporated in an RuO sphere for HER and OER, in which the Co single atom in the RuO sphere was confirmed by XAS, AC-STEM, and DFT. This tailoring strategy uses a Co single atom to modify the electronic structures of the surrounding Ru atoms and thereby remarkably elevates the electrocatalytic activities.

Microscopic analysis of plant-mediated silver nanoparticle toxicity in rainbow trout fish (Oncorhynchus mykiss).

Over the years, nanoscience and the application of nanomaterials have gained the attention of researchers due to their enormous application history. Especially, the application of AgNPs providing innovative solutions to a wide range of environmental issues, for instance, wastewater treatment, bioremediations, and environmental sensing. Besides all these, the environmental application of silver nanomaterials causes severe problems in the terrestrial and aquatic ecosystems.

Mechanisms underlying the wound healing and tissue regeneration properties of .

In the current study, aerial parts (leaves, stem and shoots) of were extracted with methanol and subjected to phytochemical and HPLC analysis. Agar well diffusion method was used for anti-bacterial activity against Gram-negative strains , , , and Gram-positive , Methicillin-resistant . Burn was induced through flame heated metal rod on mice.

Molecular Mechanisms of Complement System Proteins and Matrix Metalloproteinases in the Pathogenesis of Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is an eye disorder affecting predominantly the older people above the age of 50 years in which the macular region of the retina deteriorates, resulting in the loss of central vision. The key factors associated with the pathogenesis of AMD are age, smoking, dietary, and genetic risk factors. There are few associated and plausible genes involved in AMD pathogenesis.

BBS5 and INPP5E mutations associated with ciliopathy disorders in families from Pakistan.

Ciliopathies are a clinically and genetically heterogeneous group of disorders often exhibiting phenotypic overlap and caused by abnormalities in the structure or function of cellular cilia. As such, a precise molecular diagnosis is important for guiding clinical management and genetic counseling. In the present study, two Pakistani families comprising individuals with overlapping clinical features suggestive of a ciliopathy syndrome, including intellectual disability, obesity, congenital retinal dystrophy, and hypogonadism (in males), were investigated clinically and genetically.

Biallelic mutations in the LPAR6 gene causing autosomal recessive wooly hair/hypotrichosis phenotype in five Pakistani families.

Background: Autosomal recessive wooly hair/hypotrichosis is an inherited disorder of hair characterized by less dense, short, and tightly curled hair on the scalp and sometimes less dense to complete absence of eyebrows and eyelashes. Autosomal recessive wooly hair/hypotrichosis phenotypes are mostly associated with pathogenic sequence variants in LIPH and LPAR6 genes.

Methods: To find out the molecular basis of the disease, five families with autosomal recessive wooly hair/hypotrichosis were recruited for genetic analysis.

Identification of CACNA1D variants associated with sinoatrial node dysfunction and deafness in additional Pakistani families reveals a clinical significance.

Sinoatrial node dysfunction and deafness (SANDD) syndrome is rare and characterized by a low heart beat and severe-to-profound deafness. Additional features include fatigue, dizziness, and episodic syncope. The sinoatrial node (SAN) drives heart automaticity and continuously regulates heart rate.

Novel digenic inheritance of PCDH15 and USH1G underlies profound non-syndromic hearing impairment.

Background: Digenic inheritance is the simplest model of oligenic disease. It can be observed when there is a strong epistatic interaction between two loci. For both syndromic and non-syndromic hearing impairment, several forms of digenic inheritance have been reported.

Molecular and in silico analyses validates pathogenicity of homozygous mutations in the NPR2 gene underlying variable phenotypes of Acromesomelic dysplasia, type Maroteaux.

Homozygous and/or heterozygous loss of function mutations in the natriuretic peptide receptor B (NPR2) have been reported in causing acromesomelic dysplasia, type Maroteaux with variable clinical features and idiopathic short stature with nonspecific skeletal deformities. On the other hand, gain of function mutations in the same gene result in overgrowth disorder suggesting that NPR2 and its ligand, natriuretic peptide precursor C (CNP), are the key players of endochondral bone growth. However, the precise mechanism behind phenotypic variability of the NPR2 mutations is not fully understood so far.

Sequence variants in nine different genes underlying rare skin disorders in 10 consanguineous families.

Background: Genodermatoses represent genetic anomalies of skin tissues including hair follicles, sebaceous glands, eccrine glands, nails, and teeth. Ten consanguineous families segregating various genodermatosis phenotypes were investigated in the present study.

Methods: Homozygosity mapping, exome, and Sanger sequencing were employed to search for the disease-causing variants in the 10 families.

Sequence variants in four genes underlying Bardet-Biedl syndrome in consanguineous families.

Purpose: To investigate the molecular basis of Bardet-Biedl syndrome (BBS) in five consanguineous families of Pakistani origin.

Methods: Linkage in two families (A and B) was established to on chromosome 4q27, in family C to on chromosome 14q32.1, and in family D to on chromosome 12q21.