Use of Whole-Exome Sequencing and Pedigree Analysis to Identify X-linked Hypophosphatemia in Saudi Arabian Families.

Context: X-linked hypophosphatemia (XLH) is the most common form of inherited hypophosphatemic rickets (HR), caused by pathogenic variants in the gene. Genetic diagnosis of XLH facilitates early treatment optimization, especially for patients suitable for burosumab, a recombinant anti-fibroblast growth factor-23 monoclonal antibody.

Objective: This study aimed to use whole-exome sequencing (WES) and pedigree analysis to identify patients with XLH.

Clinical characteristics and long-term management for patients with vitamin D-dependent rickets type II: a retrospective study at a single center in Saudi Arabia.

Introduction: Hereditary Vitamin D-dependent rickets type II (HVDDR-type II) is a rare autosomal recessive disorder caused by molecular variation in the gene encoding the vitamin D receptor (VDR). This study aims to evaluate phenotype and genotype characteristics and long-term follow-up of the largest group of patients with (HVDDR-type II) in Saudi Arabia.

Methodology: We conducted a retrospective chart review to collect the clinical, biochemical, and genetic data for all HVDDR-type II patients currently receiving treatment at King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.

Experience of X-linked hypophosphatemic rickets in the Gulf Cooperation Council countries: case series.

Summary: X-linked hypophosphatemic rickets (XLH), the most prevalent form of inherited hypophosphatemic rickets, is caused by loss-of-function mutations in the gene encoding phosphate-regulating endopeptidase homolog, X-linked (PHEX). This case series presents 14 cases of XLH from Gulf Cooperation Council (GCC) countries. The patients' medical history, biochemical and radiological investigative findings, as well as treatment responses and side effects from both conventional and burosumab therapy, are described.

Information needs on type 1 diabetes mellitus (T1DM) and its management in children and adolescents: a qualitative study.

Objective: The objective of this study is to explore the information needs related to insulin therapy in children and adolescents with type 1 diabetes mellitus (T1DM) from the children's perspectives as well as their caregivers.

Design: Qualitative study; semistructured interviews. To identify emerging themes relating to information needs, open coding and thematic analysis were employed.

Modern approaches to the management of homozygous familial hypercholesterolemia in the Middle East and North Africa.

Homozygous familial hypercholesterolaemia (HoFH) is a severe form of FH in which inheritance of two defective or null mutations in genes associated with metabolism of low-density lipoprotein cholesterol (LDL-C) results in extremely high LDL-C, premature atherosclerotic cardiovascular disease (ASCVD) and mortality. Treatment of HoFH comprises a multi-modal approach of statins, ezetimibe, lipoprotein apheresis; and inhibitors of proprotein convertase subtilisin/kexin type, angiopoietin-like protein 3 (ANGPTL3) and microsomal triglyceride transfer protein. These treatments are generally costly, and patients also often require treatment for ASCVD consequent to HoFH.

Hajdu-Cheney syndrome with a novel variant in NOTCH2 gene: A case report.

Introduction: Hajdu-Cheney syndrome is a rare disorder caused by truncation mutations in exon 34 of the NOTCH2 gene. The main presentation includes acro-osteolysis, osteoporosis, and dysmorphism. This syndrome affects the other body systems as well.

The clinical characteristics and quality of life of 248 pediatric and adult patients with Congenital Adrenal Hyperplasia.

Background: Congenital Adrenal Hyperplasia (CAH) is a chronic disease that requires lifelong treatment. Patients may face stigmatization, which may affect their quality of life (QoL). Therefore, we assessed the clinical characteristics and QoL of patients with CAH in the Middle East.

A Rare Case of Adenosine Deaminase tRNA-Specific 3 Mutation, Adrenal Insufficiency, and Rhabdomyolysis.

Adenosine deaminase t-RNA-specific 3 (ADAT3) gene, present on chromosome 19, encodes for an enzyme responsible for deamination of adenosine to inosine. Individuals with ADAT3 mutation display microcephaly, dysmorphic features, neurological, behavioural, and endocrinal pathologies. ADAT3 mutation is a recognized cause of intellectual disability (ID) in Saudi Arabia, particularly amongst consanguineous families.

A Unique Genotype of Pseudohypoaldosteronism Type 1b in a Highly Consanguineous Population.

Context: Pseudohypoaldosteronism (PHA) is a condition in which serum aldosterone level is normal or elevated but its action is deficient.

Objective: This study describes the molecular genetics of PHA 1b in the highly consanguineous population of 2 Arabian Gulf countries, Saudi Arabia and Oman.

Methods: This study enrolled 22 patients from 13 unrelated families (2 families with 5 patients from Oman and 11 families with 17 patients from Saudi Arabia).

25-Hydroxylase vitamin D deficiency in 27 Saudi Arabian subjects: a clinical and molecular report on CYP2R1 mutations.

Vitamin D deficiency remains a major cause of rickets worldwide. Nutritional factors are the major cause and less commonly, inheritance causes. Recently, CYP2R1 has been reported as a major factor for 25-hydroxylation contributing to the inherited forms of vitamin D deficiency.

Molecular genetics of disorders of sex development in a highly consanguineous population.

Unlabelled: Consanguinity increases the risk of hereditary diseases including disorders of sex development (DSD). There are minimal data on DSD in the highly consanguineous population of Saudi Arabia. This study reports the molecular genetics of a series of patients with different types of DSD.

Analysis of transcript-deleterious variants in Mendelian disorders: implications for RNA-based diagnostics.

Background: At least 50% of patients with suspected Mendelian disorders remain undiagnosed after whole-exome sequencing (WES), and the extent to which non-coding variants that are not captured by WES contribute to this fraction is unclear. Whole transcriptome sequencing is a promising supplement to WES, although empirical data on the contribution of RNA analysis to the diagnosis of Mendelian diseases on a large scale are scarce.

Results: Here, we describe our experience with transcript-deleterious variants (TDVs) based on a cohort of 5647 families with suspected Mendelian diseases.

The morbid genome of ciliopathies: an update.

Purpose: Ciliopathies are highly heterogeneous clinical disorders of the primary cilium. We aim to characterize a large cohort of ciliopathies phenotypically and molecularly.

Methods: Detailed phenotypic and genomic analysis of patients with ciliopathies, and functional characterization of novel candidate genes.

Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.

We report the results of clinical exome sequencing (CES) on >2,200 previously unpublished Saudi families as a first-tier test. The predominance of autosomal-recessive causes allowed us to make several key observations. We highlight 155 genes that we propose to be recessive, disease-related candidates.