Clinical and genetic characterization of a progressive RBL2-associated neurodevelopmental disorder.

Retinoblastoma (RB) proteins are highly conserved transcriptional regulators that play important roles during development by regulating cell-cycle gene expression. RBL2 dysfunction has been linked to a severe neurodevelopmental disorder. However, to date, clinical features have only been described in six individuals carrying five biallelic predicted loss of function (pLOF) variants.

Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders.

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.

Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analysed detailed clinical and genetic data for all individuals.

The Mutational Landscape Of Genetic Cholestatic Diseases In Pakistani Children.

Objectives: To report the mutational landscape of a clinically diagnosed cohort of paediatric patients with cholestasis liver diseases.

Methods: The retrospective study was conducted at the University of Child Health Sciences, The Children Hospital, Lahore, Pakistan, from December 10, 2021, to March 31, 2022, and comprised data collected from the Paediatric Gastroenterology and Hepatology unit on demographics, clinical and laboratory findings related to children of either gender aged <12 years and diagnosed with cholestatic liver disease from July 2018 to June 2021. The diagnosis was based on clinical and biochemical findings, with no evidence of biliary atresia and metabolic liver disease.

Clinical and Genetic Description of Hereditary Chronic Pancreatitis in Pakistani Children.

Background/aims: The purpose of this study was to identify the spectrum and frequency of pathogenic variants as well as the clinical and genetic insight of hereditary chronic pancreatitis in Pakistani children.

Materials And Methods: The deoxyribonucleic acid of affected probands of 44 unrelated Pakistani families, having hereditary chronic pancreatitis-affected children, were subjected to massive parallel sequencing for candidate reported genes (SPINK1, PRSS1, CFTR, CPA1, CTRC, CBS, AGL, PHKB, and LPL). Data were analyzed using different bioinformatics tools for the variants and in-silico analysis.

A transposase-derived gene required for human brain development.

DNA transposable elements and transposase-derived genes are present in most living organisms, including vertebrates, but their function is largely unknown. PiggyBac Transposable Element Derived 5 (PGBD5) is an evolutionarily conserved vertebrate DNA transposase-derived gene with retained nuclease activity in human cells. Vertebrate brain development is known to be associated with prominent neuronal cell death and DNA breaks, but their causes and functions are not well understood.

Clinical spectrum and diagnostic challenges of vitamin D dependent rickets type 1A (VDDR1A) caused by mutation in resource limited countries.

Objectives: Vitamin D dependent rickets type 1A (VDDR1A) is a rare autosomal recessive condition due to inactivating mutation of . It mimics clinically, biochemically and rediologically to nutritional and hypophosphatemic rickets. In developing countries like Pakistan, VDDR1A is often misdiagnosed as nutritional rickets or hypophosphatemic rickets due lack of free access to 1,25 (OH) 2 D level and genetic testing.

Management challenges of Rabson Mendenhall syndrome in a resource limited country: a case report.

Objectives: Rabson Mendenhall syndrome  (RMS) is a rare form of insulin resistance syndrome caused by insulin receptor mutation. In term of severity, it lies at an intermediate point on spectrum of insulin resistance with Donohue syndrome flanking the severe and Type A insulin resistance at the mild end. We are reporting a 3.

Very early onset inflammatory bowel disease: Spectrum of clinical presentation, diagnostic tools and outcome in children.

Objective: To explore the spectrum of presentation, underlying monogenetic defects and outcome in very early onset inflammatory bowel disease (VEO-IBD).

Method: The prospective, observational study was conducted at the Children's Hospital, Lahore, Pakistan, from January 2017 to December 2018, and comprised children developing features of inflammatory bowel disease aged <6 years. Data included demography, clinical presentation, diagnostic tools and outcome.

Genomic testing in 1019 individuals from 349 Pakistani families results in high diagnostic yield and clinical utility.

We implemented a collaborative diagnostic program in Lahore (Pakistan) aiming to establish the genetic diagnosis, and to asses diagnostic yield and clinical impact in patients with suspected genetic diseases. Local physicians ascertained pediatric patients who had no previous access to genetic testing. More than 1586 genetic tests were performed in 1019 individuals (349 index cases, 670 relatives).

Variability of clinical and biochemical phenotype in liver phosphorylase kinase deficiency with variants in the phosphorylase kinase (PHKG2) gene.

Background PHKG2-related liver phosphorylase kinase deficiency is inherited in autosomal recessive pattern and is a rare type of liver glycogenosis. We demonstrated the clinical presentation and genetic determinants involved in children with PHKG2- related liver phosphorylase kinase deficiency. Methodology Ten Pakistani children with liver phosphorylase kinase from seven different families, were enrolled over a period of 18 months.

Mutational spectrum of gene in Pakistani Niemann-Pick disease patients.

Objective: Genetic variation analysis of rare autosomal recessive Niemann-Pick disease (NPD) Pakistani patients.

Methods: We sequenced the gene including its all coding and flanking regions in seven unrelated sporadic patients suffering from Niemann-Pick disease through targeted exome sequencing. Genetic variants mapping and their protein predictions were evaluated using different bioinformatics tools and clinical phenotypes were correlated.

Mapping of IDUA gene variants in Pakistani patients with mucopolysaccharidosis type 1.

Background Mucopolysaccharidosis type 1 (MPS1) is a rare debilitating multisystem lysosomal disorder resulting due to the deficiency of α-L-iduronidase enzyme (IDUA), caused by recessive mutations in the IDUA gene. Lack or improper amount of the IDUA enzyme results in the improper metabolism of mucopolysaccharides or glycosaminoglycans (GAGs). These large sugar molecules accumulate in lysosomes within cells leading to different systemic complications.

Clinical Spectrum Of Solitary Rectal Ulcer In Children Presenting With Per-Rectal Bleed.

Background: Solitary rectal ulcer syndrome (SRUS) is a benign and chronic disorder well known in young adults and less common in children. The objective of this study was to determine the frequency and clinical spectrum of solitary rectal ulcer in children with bleeding per rectum.

Methods: This study was conducted in the Department of Paediatric Gastroenterology Hepatology& Nutrition; The Children's Hospital & The Institute of Child Health, Lahore, from January-December 2015.

Coronary grafts flow and cardiac pacing modalities: how to improve perioperative myocardial perfusion.

Objective: Aim of this study was to investigate modifications of coronary grafts flow during different pacing modalities after CABG.

Materials And Methods: Two separate prospective studies were conducted in patients undergoing CABG and requiring intraoperative epicardial pacing. In a first study (22 patients) coronary grafts flows were measured during dual chamber pacing (DDD) and during ventricular pacing (VVI).