ELFN1 deficiency: The mechanistic basis and phenotypic spectrum of a neurodevelopmental disorder with epilepsy.

Purpose: Synaptic communication deficits are central to many neurodevelopmental disorders. However, for rare monogenic conditions, these disorders remain poorly defined, with limited understanding of their molecular etiology. A homozygous frameshift variant in the synaptic cell adhesion molecule ELFN1 was reported in a family with 3 affected siblings with epileptic encephalopathy, alongside a missense variant of uncertain significance in a cohort study involving a family with intellectual disability.

Risk Factors for the Development of Early Onset Diabetes in the Population of Sindh Province, Pakistan.

: Early-onset diabetes (EOD), diagnosed at ≤35 years, is a growing public health crisis in low- and middle-income countries, including Pakistan. Identifying modifiable and non-modifiable risk factors is critical for developing effective prevention strategies. This study aimed to investigate the risk factors associated with EOD in Sindh, Pakistan, focusing on genetic, lifestyle, and metabolic determinants.

Bi-allelic variants in BRF2 are associated with perinatal death and craniofacial anomalies.

Background: Variants in genes encoding multiple subunits of the RNA Polymerase III complex which synthesizes rRNAs, tRNAs, and other small RNAs were previously associated with neurological disorders, such as syndromic hypomyelination leukodystrophies, pontocerebellar hypoplasia, and cerebellofaciodental syndrome. One new such candidate is BRF2, which encodes a TFIIB-like factor that recruits the RNA polymerase III complex to type 3 promoters to initiate transcription of U6, RnaseP, and 7SK RNAs.

Methods: We combined sequencing with functional analyses to investigate the effects of BRF2 variants.

A comprehensive genetic landscape of inherited retinal diseases in a large Pakistani cohort.

Inherited retinal diseases (IRDs) are a group of rare Mendelian disorders that often result in progressive vision loss and potentially to complete blindness at the end stage. In this study, we investigated a large cohort of patients with IRDs from Pakistan, the world's fifth most populous country, which is also characterized by distinctive demographic features, such as a high prevalence of consanguinity, endogamy, and a wide variety of ethnic groups. Specifically, we examined a total of 213 unrelated families (722 affected individuals) from three very large geographical regions.

Construction of 2D/2D α-FeO/g-CN Z-scheme photocatalysts with SnO as an energy platform for directed charge transfer in cascade heterojunction: Photocatalytic CO reduction and pollutant degradation.

Developing an efficient visible-light-driven photocatalysts for conversion of atmospheric CO into valuable fuels is a promising strategy to mitigate the escalating greenhouse gas, environmental, and energy crisis. This study presents an innovative design for a cascade Z-scheme comprising of dimensional matched SnO-α-FeO/g-CN (SO-FO/CN) nanosheets heterojunction. In this configuration, SnO functions as an optimal energy platform that not only facilitates charge transfer and separation but also sustains sufficient thermodynamic energy for redox reactions and inhibits the undesired type-II charge transfer pathway.

Deciphering the Genetic Basis of Degenerative and Developmental Eye Disorders in 50 Pakistani Consanguineous Families Using Whole-Exome Sequencing.

Degenerative and developmental eye disorders, including inherited retinal dystrophies (IRDs), anophthalmia, and congenital cataracts arise from genetic mutations, causing progressive vision loss or congenital structural abnormalities. IRDs include a group of rare, genetically, and clinically heterogeneous retinal diseases. It is caused by variations in at least 324 genes, affecting numerous retinal regions.

A Novel Biallelic Variant in IHH Causing Acrocapitofemoral Dysplasia in a Pakistani Family.

Background: Acrocapitofemoral dysplasia (ACFD) is a rare autosomal recessive disorder, characterized by postnatal onset of disproportionate short stature with short limbs, brachydactyly, cone-shaped epiphysis, narrow thorax, and relatively large head. To date, only three homozygous missense mutations have been reported in the signaling amino terminal domain (201-308 amino acids) of the IHH gene in three ACFD families from Belgian, Dutch, and Turkish ethnicities.

Methods: In the present study, we have investigated two patients in a Pakistani family affected with ACFD.

Bi-allelic variants in MRPL49 cause variable clinical presentations, including sensorineural hearing loss, leukodystrophy, and ovarian insufficiency.

Combined oxidative phosphorylation deficiency (COXPD) is a rare multisystem disorder that is clinically and genetically heterogeneous. Genome sequencing identified bi-allelic MRPL49 variants in individuals from nine unrelated families with presentations ranging from Perrault syndrome (primary ovarian insufficiency and sensorineural hearing loss) to severe childhood onset of leukodystrophy, learning disability, microcephaly, and retinal dystrophy. Complexome profiling of fibroblasts from affected individuals revealed reduced levels of the small mitochondrial ribosomal subunits and a more pronounced reduction of the large mitochondrial ribosomal subunits.

Long-term impact of different prevalent cropping systems on soil physico-chemical characteristics under subtropical climate conditions of Punjab, Pakistan.

Lack of site-specific nutrients information for different cropping systems has been a major challenge in addressing declining soil fertility levels and enhance crop productivity in Punjab, Pakistan. Therefore, the study was designed to assess and quantify soil physico-chemical characteristics, crop yield and economic feasibility of different cropping systems (CS), including groundnut-wheat (G-W), rice-wheat (R-W), fallow-gram/wheat (F-G/W), mix cropping (Mix C) and cotton-wheat (C-W). A total of 470 georeferenced soil samples were collected using a random survey approach, and the samples were analyzed for soil texture, pH, electrical conductivity (EC), organic matter percentage (OM), total nitrogen percentage (TN), accessible phosphorus (AvP) (mg kg) and extractable potassium (ExK) (mg kg).

Recurrent Gastrointestinal Symptoms and Diagnosis of Superior Mesenteric Artery Syndrome.

This is a case of a young lady who was admitted multiple times with complaints of inability to digest food and abdominal pain. She had nausea and vomiting for long periods and was unable to tolerate orally. As she was unable to tolerate oral feeding and losing weight, she was started on nasogastric feed (NG feed) and later percutaneous endoscopic gastrostomy (PEG) tube feeding because NG feed was uncomfortable for the patient and did not alleviate the problem.

A novel homozygous missense variant in causes cone dystrophy in a consanguineous Pakistani family.

Background: Cone dystrophy is a heterogeneous hereditary retinal disorder with disease symptoms appearing in the late first or early second decades of life.

Methods: A consanguineous Pakistani family with three affected individuals underwent detailed clinical and genetic investigation.

Results: The proband, a 63-years old male, showed severely reduced day vision, a visual acuity of counting fingers (CF), color vision deficiency, high myopia and photophobia.

Ultrasound shear wave elastography of the placenta: a potential tool for early detection of fetal growth restriction.

Background: Sonographic placental elastography has recently been employed as a non-invasive tool to investigate the structural alterations associated with various conditions such as pre-eclampsia, gestational diabetes and fetal growth restriction (FGR). The study was conducted based on the hypothesis that the placental elasticity might differ with varying severity of FGR and with that of appropriate for gestational age (AGA) pregnancies.

Methods: This study involved 121 pregnant women, with 54 in the normal group and 67 in the FGR group, which was defined as the fetal weight below the 10th percentile for gestational age.

Biallelic variants in cause variable clinical presentations, including sensorineural hearing loss, leukodystrophy, and ovarian insufficiency.

Combined oxidative phosphorylation deficiency (COXPD) is a rare multisystem disorder which is clinically and genetically heterogeneous. Genome sequencing identified biallelic variants in individuals from five unrelated families with presentations ranging from Perrault syndrome (primary ovarian insufficiency and sensorineural hearing loss) to severe childhood onset of leukodystrophy, learning disability, microcephaly and retinal dystrophy. Complexome profiling of fibroblasts from affected individuals revealed reduced levels of the small and, a more pronounced reduction of, the large mitochondrial ribosomal subunits.

The genetic cause of neurodevelopmental disorders in 30 consanguineous families.

Objective: This study aims to clinically and genetically assess 30 unrelated consanguineous Pakistani families from various ethnic backgrounds, all exhibiting features of neurodevelopmental disorders (NDDs).

Methods: We conducted clinical, genetic, biochemical, and molecular analyses on 30 consanguineous families with NDDs enrolled from various regions of Pakistan. The likely molecular causes of primary microcephaly and NDDs were identified.

Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression.

Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.

Next-generation sequencing to genetically diagnose a diverse range of inherited eye disorders in 15 consanguineous families from Pakistan.

Inherited retinal dystrophies (IRDs) are characterized by photoreceptor dysfunction or degeneration. Clinical and phenotypic overlap between IRDs makes the genetic diagnosis very challenging and comprehensive genomic approaches for accurate diagnosis are frequently required. While there are previous studies on IRDs in Pakistan, causative genes and variants are still unknown for a significant portion of patients.

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.

Performance evaluation of gravity-driven bioreactor (GDB) for simultaneous treatment of black liquor and domestic wastewater.

A lab-scale gravity-driven bioreactor (GDB) was designed and constructed to evaluate the simultaneous treatment of black liquor and domestic wastewater. The GDB was operated with a mixture of black liquor and domestic wastewater at a ratio of 1:1 and maintained at an average organic loading rate of 1235 mg-COD/L-Day. The wastewater was fed to the primary sedimentation tank at a flow rate of approximately 12 mL/min and subsequently passed through serially connected anaerobic and aerobic chambers with the same flow rate.

A loss of function variant in AGPAT3 underlies intellectual disability and retinitis pigmentosa (IDRP) syndrome.

Intellectual disability (ID) and retinal dystrophy (RD) are the frequently found features of multiple syndromes involving additional systemic manifestations. Here, we studied a family with four members presenting severe ID and retinitis pigmentosa (RP). Using genome wide genotyping and exome sequencing, we identified a nonsense variant c.

Combined Single Gene Testing and Genome Sequencing as an Effective Diagnostic Approach for Anophthalmia and Microphthalmia Patients.

Anophthalmia and microphthalmia (A/M) are among the most severe congenital developmental eye disorders. Despite the advancements in genome screening technologies, more than half of A/M patients do not receive a molecular diagnosis. We included seven consanguineous families affected with A/M from Pakistani cohort and an unknown molecular basis.

Characterization of Vps13b-mutant mice reveals neuroanatomical and behavioral phenotypes with females less affected.

The vacuolar protein sorting-associated protein 13B (VPS13B) is a large and highly conserved protein. Disruption of VPS13B causes the autosomal recessive Cohen syndrome, a rare disorder characterized by microcephaly and intellectual disability among other features, including developmental delay, hypotonia, and friendly-personality. However, the underlying mechanisms by which VPS13B disruption leads to brain dysfunction still remain unexplained.