Biallelic null variants in PNPLA8 cause microcephaly by reducing the number of basal radial glia.

Patatin-like phospholipase domain-containing lipase 8 (PNPLA8), one of the calcium-independent phospholipase A2 enzymes, is involved in various physiological processes through the maintenance of membrane phospholipids. Biallelic variants in PNPLA8 have been associated with a range of paediatric neurodegenerative disorders. However, the phenotypic spectrum, genotype-phenotype correlations and the underlying mechanisms are poorly understood.

Novel Presentation of Major Histocompatibility Complex Class II Deficiency with Hemophagocytic Lymphohistiocytosis.

Purpose: Major histocompatibility complex (MHC) class II deficiency is one of the combined immune deficiency disorders caused by defects in the MHC class II regulatory genes leading to abnormal T cells development and function. Therefore, patients mainly present with increased susceptibility to infections, diarrhea, and failure to thrive. In this report, we present one MHC class II deficient patient with a novel presentation with Hemophagocytic Lymphohistiocytosis (HLH).

Risk factors predicting disease severity and mortality in coronavirus disease 2019 Saudi Arabian patients.

Context: Coronavirus disease 2019 (COVID-19) became a global pandemic that may be associated with significant associated risk factors.

Aims: The aim of this study was to evaluate the factors predisposing risk to death in COVID-19 patients.

Settings And Design: This is a retrospective study that presents the demographic, clinical presentation, and laboratory findings on our patients to determine risk factors contributing to their COVID-19 outcome.

Age/BMI is a Stronger Predictor of Death in COVID-19 Patients than Age Alone: A Pilot Study.

The objective of this study was to investigate the effect of age and BMI on the risk of death in patients with coronavirus disease 2019 (COVID-19). A cohort of 206 Saudi COVID-19 patients was included in this study. Data on age, BMI, hospitalization, comorbidities, and death were collected and analyzed.

Prevalence of Associated Endocrine Diseases in Patients with Neurofibromatosis Type 1.

 Neurofibromatosis type 1 (NF-1) is an autosomal dominant neurocutaneous disorder that increases the risk of developing benign and malignant tumors. Several associated endocrine diseases in NF-1 patients have been explained in the literature. Thus, this study aims to assess the endocrine manifestations as there no previous local data have discussed this association.

Identification of CSF3R Mutations in B-Lineage Acute Lymphoblastic Leukemia Using Comprehensive Cancer Panel and Next-Generation Sequencing.

B-lineage acute lymphocytic leukemia (B-ALL) is characterized by different genetic aberrations at a chromosomal and gene level which are very crucial for diagnosis, prognosis and risk assessment of the disease. However, there is still controversial arguments in regard to disease outcomes in specific genetic abnormalities, e.g.

Identification of Novel Mutations in Colorectal Cancer Patients Using AmpliSeq Comprehensive Cancer Panel.

Biomarker discovery would be an important tool in advancing and utilizing the concept of precision and personalized medicine in the clinic. Discovery of novel variants in local population provides confident targets for developing biomarkers for personalized medicine. We identified the need to generate high-quality sequencing data from local colorectal cancer patients and understand the pattern of occurrence of variants.

CRISPR/Cas9 Knockout Stimulates the Insulin Secretion Pathway Leading to Excessive Insulin Secretion.

Aim: Despite the enormous efforts to understand Congenital hyperinsulinism (CHI), up to 50% of the patients are genetically unexplained. We aimed to functionally characterize a novel candidate gene in CHI.

Patient: A 4-month-old boy presented severe hyperinsulinemic hypoglycemia.

Clinical course of myeloproliferative leukaemia virus oncogene (MPL) mutation-associated familial thrombocytosis: a review of 64 paediatric and adult patients.

Familial thrombocytosis (FT) is a rare hereditary haematological disorder characterised by increased platelet count, usually caused by germ-line mutations in thrombopoietin (THPO), myeloproliferative leukaemia virus oncogene (MPL) or Janus kinase 2 (JAK2) genes, and can be associated with increased risk of thrombosis. We aimed to determine the yield of diagnostic tests, assess treatment received and describe the clinical course of MPL-associated FT. We retrospectively reviewed all paediatric and adult haematology patients diagnosed with MPL-related FT, who were seen in our clinics from March 2013 to February 2021.

Isolation and Establishment of a Highly Proliferative, Cancer Stem Cell-Like, and Naturally Immortalized Triple-Negative Breast Cancer Cell Line, KAIMRC2.

In vitro studies of a disease are key to any in vivo investigation in understanding the disease and developing new therapy regimens. Immortalized cancer cell lines are the best and easiest model for studying cancer in vitro. Here, we report the establishment of a naturally immortalized highly tumorigenic and triple-negative breast cancer cell line, KAIMRC2.

The Leukodystrophy Spectrum in Saudi Arabia: Epidemiological, Clinical, Radiological, and Genetic Data.

Leukodystrophies (LDs) are inherited heterogeneous conditions that affect the central nervous system with or without peripheral nerve involvement. They are individually rare, but collectively, they are common. Thirty disorders were included by the Global Leukodystrophy Initiative Consortium (GLIA) as LDs.

A novel gene in early childhood diabetes: EDEM2 silencing decreases SLC2A2 and PXD1 expression, leading to impaired insulin secretion.

Monogenic diabetes is a rare type of diabetes resulting from mutations in a single gene. To date, most cases remain genetically unexplained, posing a challenge for accurate diabetes treatment, which leads to on a molecular diagnosis. Therefore, a trio exome scan was performed in a lean, nonsyndromic Caucasian girl with diabetes onset at 2½ years who was negative for autoantibodies.

Late-onset multiple venous malformations confined to the upper limb: link to somatic mutations.

Venous (cavernous) malformations are commonly seen in the upper limb. Almost all venous malformations are congenital. They may be sporadic, familial, or syndromic.

Exome sequencing revealed DNA variants in NCOR1, IGF2BP1, SGLT2 and NEK11 as potential novel causes of ketotic hypoglycemia in children.

Unexplained or idiopathic ketotic hypoglycemia (KH) is the most common type of hypoglycemia in children. The diagnosis is based on the exclusion of routine hormonal and metabolic causes of hypoglycemia. We aimed to identify novel genes that cause KH, as this may lead to a more targeted treatment.

Proteomic and Molecular Assessment of the Common Saudi Variant in Gene Through Mesenchymal Stem Cells.

Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) is a coenzyme encoded by that converts very-long-chain fatty acids into energy. This process is disrupted by c.65C > A; p.

A novel interstitial deletion of chromosome 2q21.1-q23.3: Case report and literature review.

Background: Interstitial deletions of 2q are rare. Those that have been reported show varying clinical manifestations according to the size of the deletion and the genomic region involved.

Method And Results: We describe a preterm male harboring a novel interstitial deletion encompassing the 2q21.

Oxidative stress, caloric intake and outcomes of critically ill patients.

Background: The aim of this study was to investigate the patterns of oxidative stress in critically ill patients and the association with caloric intake and outcomes.

Methods: In this pre-planned sub-study of the PermiT (Permissive Underfeeding versus Target Enteral Feeding in Adult Critically Ill Patients Trial- ISRCTN68144998), we included patients expected to stay in the ICU for ≥14 days. Serum samples were collected on days 1, 3, 5, 7 and 14 of enrollment.

Permissive underfeeding, cytokine profiles and outcomes in critically ill patients.

Background: During critical illness in humans, the effects of caloric restriction on the inflammatory response are not well understood. The aim of this study is to examine the associations of caloric restriction, inflammatory response profiles and outcomes in critically ill patients.

Methods: This is a sub-study of the PermiT trial (Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults Trial- ISRCTN68144998).

Differential Gene Expression in Peripheral White Blood Cells with Permissive Underfeeding and Standard Feeding in Critically Ill Patients: A Descriptive Sub-study of the PermiT Randomized Controlled Trial.

The effect of short-term caloric restriction on gene expression in critically ill patients has not been studied. In this sub-study of the PermiT trial (Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults Trial- ISRCTN68144998), we examined gene expression patterns in peripheral white blood cells (buffy coat) associated with moderate caloric restriction (permissive underfeeding) in critically ill patients compared to standard feeding. Blood samples collected on study day 1 and 14 were subjected to total RNA extraction and gene expression using microarray analysis.

Prevalence of BRCA1 and BRCA2 Mutations Among High-Risk Saudi Patients With Breast Cancer.

Purpose Over the past three decades, the incidence rate of breast cancer (BC) among Arab women has continually increased. However, data on the prevalence of BRCA1/2 mutations are scarce. Although the population in Saudi Arabia is at large homogeneous and consanguinity is common, especially in the central, eastern, and southern regions of the country, the prevalence of BRCA1 and BRCA2 mutations and the characteristics of BC are not well studied in the country.

KIF16B is a candidate gene for a novel autosomal-recessive intellectual disability syndrome.

Intellectual disability (ID) and global developmental delay are closely related; the latter is reserved for children under the age of 5 years as it is challenging to reliably assess clinical severity in this population. ID is a common condition, with up to 1%-3% of the population being affected and leading to a huge social and economic impact. ID is attributed to genetic abnormalities most of the time; however, the exact role of genetic involvement in ID is yet to be determined.

Coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma with antecedent chronic lymphocytic leukemia: a case report and review of the literature.

Background: Chronic lymphocytic leukemia and chronic myeloid leukemia are the most common types of adult leukemia. However, it is rare for the same patient to suffer from both. Richter's transformation to diffuse large B-cell lymphoma is frequently observed in chronic lymphocytic leukemia.

Isolation and characterization of a new naturally immortalized human breast carcinoma cell line, KAIMRC1.

Background: Breast cancer is one of the most common cancer and a leading cause of death in women. Up to date the most commonly used breast cancer cell lines are originating from Caucasians or Afro-Americans but rarely cells are being derived from other ethnic groups. Here we describe for the first time the establishment of a naturally transformed breast cancer cell line, KAIMRC1 from an Arab woman of age 62 suffering from stage IIB breast cancer (T2N1M0).