A5059328280- Metabolism and Genetic Disorders
- Genomics and Rare Diseases
- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- RNA modifications and cancer
- Neonatal Health and Biochemistry
- interferon and immune responses
- Hedgehog Signaling Pathway Studies
- Hemoglobinopathies and Related Disorders
- Congenital limb and hand anomalies
- Neurogenetic and Muscular Disorders Research
- Fetal and Pediatric Neurological Disorders
- Ubiquitin and proteasome pathways
- Biochemical and Molecular Research
- Diet and metabolism studies
- Genetic factors in colorectal cancer
- Peptidase Inhibition and Analysis
- Microtubule and mitosis dynamics
- Lysosomal Storage Disorders Research
- ATP Synthase and ATPases Research
- Methemoglobinemia and Tumor Lysis Syndrome
- Endoplasmic Reticulum Stress and Disease
- Biomedical Research and Pathophysiology
- RNA regulation and disease
King Abdulaziz Medical City
2015-2024
King Saud bin Abdulaziz University for Health Sciences
2015-2024
King Abdullah International Medical Research Center
2017-2024
National Guard Health Affairs
2010-2024
National Center on Birth Defects and Developmental Disabilities
2011
King Saud University
2009
King Fahad Hospital Jeddah
2003-2008
Johns Hopkins University
1998-2000
Virginia Commonwealth University
2000
California State University, Northridge
2000
We report our results of 1000 diagnostic WES cases based on 2819 sequenced samples from 54 countries with a wide phenotypic spectrum. Clinical information given by the requesting physicians was translated to HPO terms. processes were performed according standardized settings. identified underlying pathogenic or likely variants in 307 families (30.7%). In further 253 (25.3%) variant unknown significance, possibly explaining clinical symptoms index patient identified. enabled timely diagnosing...
Nuclear genetic disorders causing mitochondrial DNA (mtDNA) depletion are clinically and genetically heterogeneous, the molecular etiology remains undiagnosed in majority of cases. Through whole-exome sequencing, we identified recessive nonsense splicing mutations FBXL4 segregating three unrelated consanguineous kindreds which affected children present with a fatal encephalopathy, lactic acidosis, severe mtDNA muscle. We show that is an F-box protein colocalizes mitochondria loss-of-function...
PurposeThe application of genomic sequencing to investigate unexplained death during early human development, a form lethality likely enriched for severe Mendelian disorders, has been limited.MethodsIn this study, we employed exome as molecular autopsy tool in cohort 44 families with at least one or lethal fetal malformation any stage utero development. Where no DNA was available from the fetus, performed by proxy, i.e., through parental testing.ResultsPathogenic pathogenic variants were...
Abstract Despite clear technical superiority of genome sequencing (GS) over other diagnostic methods such as exome (ES), few studies are available regarding the advantages its clinical application. We analyzed 1007 consecutive index cases for whom GS was performed in a setting 2-year period. reported pathogenic and likely (P/LP) variants that explain patients’ phenotype 212 (21.1%). In 245 additional (24.3%), variant unknown significance (VUS) related to reported. especially investigated...
To address the implementation of National Newborn Screening Program (NBS) in Saudi Arabia and stratify incidence screened disorders.A retrospective study conducted between 1 August 2005 31 December 2012, total 775 000 newborns were from 139 hospitals distributed among all regions Arabia. The NBS screens for 16 disorders a selective list inborn errors metabolism (IEM) endocrine disorders. Heel prick dry blood spot samples obtained biochemical immunoassay testing. Recall screening testing was...
SummaryNail-patella syndrome (NPS), a pleiotropic disorder exhibiting autosomal dominant inheritance, has been studied for >100 years. Recent evidence shows that NPS is the result of mutations in LIM-homeodomain gene LMX1B. To determine whether specific LMX1B are associated with different aspects phenotype, we screened cohort 41 families mutations. A total 25 were identified 37 families. The nature supports hypothesis haploinsufficiency There was no correlation between phenotype and Nail-patella
Abstract N-alpha-acetylation is one of the most common co-translational protein modifications in humans and essential for normal cell function. NAA10 encodes enzyme NAA10, which catalytic subunit N-terminal acetyltransferase A (NatA) complex. The auxiliary regulatory subunits NatA complex are NAA15 Huntington-interacting (HYPK), respectively. Through a genotype-first approach with exome sequencing, we identified phenotypically characterized 30 individuals from unrelated families 17 different...
The Nck-associated protein 1–like (NCKAP1L) gene, alternatively called hematopoietic 1 (HEM-1), encodes a lineage–specific regulator of the actin cytoskeleton. Nckap1l-deficient mice have anomalies in lymphocyte development, phagocytosis, and neutrophil migration. Here we report, for first time, NCKAP1L deficiency cases humans. In two unrelated patients Middle Eastern origin, recessive mutations abolishing expression led to immunodeficiency, lymphoproliferation, hyperinflammation with...
Inborn errors of metabolism (IEMs) are individually rare; however, they collectively common. More than 600 human diseases caused by inborn now recognized, and this number is constantly increasing as new concepts techniques become available for identifying biochemical phenotypes. The aim study was to determine the type distribution IEMs in patients presenting a tertiary care center Saudi Arabia.We conducted retrospective review children diagnosed with Pediatric Department King Abdulaziz...
PurposeWithin this study, we aimed to discover novel gene–disease associations in patients with no genetic diagnosis after exome/genome sequencing (ES/GS).MethodsWe followed two approaches: (1) a patient-centered approach, which routine diagnostic analysis systematically interrogates variants genes not yet associated human diseases; and (2) gene variant centered approach. For the latter, focused on de novo that presented neurodevelopmental delay (NDD) and/or intellectual disability (ID), are...
Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are severe autosomal recessive disorders associated with decreased mtDNA copy number in clinically affected tissues. The hepatocerebral form (mtDNA liver and brain) has been mutations the POLG, PEO1 (Twinkle), DGUOK MPV17 genes, latter encoding a mitochondrial inner membrane protein of unknown function. aims this study were to clarify further clinical, biochemical, cellular molecular genetic features MDS due gene mutations. We identified 12...
MICU1 encodes a Ca2+ sensing, regulatory subunit of the mitochondrial uniporter, selective calcium channel within organelle's inner membrane. entry into mitochondria helps to buffer cytosolic transients and also activates ATP production organelle. Mutations in have previously been reported 17 children from nine families with muscle weakness, fatigue, normal lactate, persistently elevated creatine kinase, as well variable features that include progressive extrapyramidal signs, learning...
Asparagine synthetase deficiency (ASD) is a newly identified neurometabolic disorder characterized by severe congenital microcephaly, global developmental delay, intractable seizure disorder, and spastic quadriplegia. Brain MRI showed brain atrophy, delayed myelination, simplified gyriform pattern.We report ASD in 2- 4-year-old sibling. On them, we described clinical, biochemical, molecular findings, compared our results with previously reported cases.We homozygous novel missense mutation...