Clinical and biochemical features associated with BCS1L mutation.

Our study describes a novel phenotype in a series of nine Saudi patients with lactic acidosis, from four consanguineous families three of which are related. Detailed genetic studies including linkage, homozygosity mapping and targeted sequencing identified a causative mutation in the BCS1L gene. All affected members of the families have an identical mutation in this gene, mutations of which are recognized causes of Björnstad syndrome, GRACILE syndrome and a syndrome of neonatal tubulopathy, encephalopathy, and liver failure (MIM 606104) leading to isolated mitochondrial respiratory chain complex III deficiency.

A novel X-linked disorder with developmental delay and autistic features.

Objective: Genomic duplications that lead to autism and other human diseases are interesting pathological lesions since the underlying mechanism almost certainly involves dosage sensitive genes. We aim to understand a novel genomic disorder with profound phenotypic consequences, most notably global developmental delay, autism, psychosis, and anorexia nervosa.

Methods: We evaluated the affected individuals, all maternally related, using childhood autism rating scale (CARS) and Vineland Adaptive scales, magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) brain, electroencephalography (EEG), electromyography (EMG), muscle biopsy, high-resolution molecular karyotype arrays, Giemsa banding (G-banding) and fluorescent in situ hybridization (FISH) experiments, mitochondrial DNA (mtDNA) sequencing, X-chromosome inactivation study, global gene expression analysis on Epstein-Barr virus (EBV)-transformed lymphoblasts, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR).

GM2 gangliosidosis in Saudi Arabia: multiple mutations and considerations for future carrier screening.

The GM2 gangliosidose, Tay-Sachs and Sandhoff diseases, are a class of lysosomal storage diseases in which relentless neurodegeneration results in devastating neurological disability and premature death. Primary prevention is the most effective intervention since no effective therapy is currently available. An extremely successful model for the prevention of GM2 gangliosidosis in the Ashkenazi Jewish community is largely attributable to the very limited number of founder mutations in that population.

Chromosome 12q24.31-q24.33 deletion causes multiple dysmorphic features and developmental delay: First mosaic patient and overview of the phenotype related to 12q24qter defects.

Background: Genomic imbalances of the 12q telomere are rare; only a few patients having 12q24.31-q24.33 deletions were reported.

Integrative and comparative genomics analysis of early hepatocellular carcinoma differentiated from liver regeneration in young and old.

Background: Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related deaths worldwide. It is often diagnosed at an advanced stage, and hence typically has a poor prognosis. To identify distinct molecular mechanisms for early HCC we developed a rat model of liver regeneration post-hepatectomy, as well as liver cells undergoing malignant transformation and compared them to normal liver using a microarray approach.

Hormonal levels of leptin, insulin, ghrelin, and neuropeptide Y in lean, overweight, and obese Saudi females.

Objective: To studied the relationship that exists between leptin, ghrelin, insulin, neuropeptide Y (NPY), anthropometric, and metabolic variables in Saudi females.

Methods: The study was conducted at the Department of Genetics, King Faisal Specialist Hospital & Research Center, Riyadh, Kingdom of Saudi Arabia from November 2004 to August 2005. One hundred and twenty-two Saudi females were divided into 3 body mass index (BMI) groups: lean (N=60), overweight (N=17), and obese (N=45).

Novel mitochondrial DNA transversion mutation in transfer ribonucleic acid for leucine 2 (CUN) in a patient with the clinical features of MELAS.

We describe an 11-year-old Saudi boy who had an encephalopathy suggestive of mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes (MELAS). We screened his entire mitochondrial DNA coding region and detected one novel transversion point mutation at nt-12299 A > C in the transfer ribonucleic acid for leucine 2 (CUN) that is located in the anticodon loop. We believe that this mutation is the cause of his disease condition.

Ophthalmic manifestations of Sanjad-Sakati syndrome.

Background: Sanjad-Sakati syndrome (SSS) is a rare disorder characterized by hypoparathyroidism, growth and developmental delay, and dysmorphism. The purpose of this report is to describe the ophthalmic manifestations of Sanjad-Sakati syndrome (SSS; hypoparathyroidism-mental retardation-dysmorphism syndrome, HRD) (OMIM 241410).

Patients: We included a total of 17 patients who were seen at two hospitals in Riyadh.

Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3.

Biotin-responsive basal ganglia disease (BBGD) is a recessive disorder with childhood onset that presents as a subacute encephalopathy, with confusion, dysarthria, and dysphagia, and that progresses to severe cogwheel rigidity, dystonia, quadriparesis, and eventual death, if left untreated. BBGD symptoms disappear within a few days with the administration of high doses of biotin (5-10 mg/kg/d). On brain magnetic resonance imaging examination, patients display central bilateral necrosis in the head of the caudate, with complete or partial involvement of the putamen.

Recently available techniques applicable to genetic problems in the Middle East.

In this paper, we address the preventive health aspects of genetic problems in the Middle East and provide guidelines to prioritize preventive strategies. Applications of various novel genetic techniques such as comprehensive neonatal screening, high throughput heterozygote detection, preimplantation genetic diagnosis, Affymetrix systems, the NanoChip system and a new way of sensitive karyotyping for single-cell chromosome abnormalities are discussed. In conclusion, from the various genetic techniques available, each country should adopt strategies most suitable to its genetic needs and should prioritize the programs to be used in prevention.

Mitochondrial DNA nucleotide changes in non-arteritic ischemic optic neuropathy.

The authors sequenced the entire mitochondrial DNA coding region in a group of 19 patients with non-arteritic anterior ischemic optic neuropathy (NAION) and in 100 controls. Synonymous and nonsynonymous nucleotide changes were more common in NAION patients (p < 0.001).

Carnitine prevents cyclic GMP-induced inhibition of peroxisomal enzyme activities.

Peroxisomes, also termed as microbodies, are now known to carry out several specialized metabolic activities that are vital to cellular function. A defect in peroxisomal function leads to development of a fatal human disease, and a number of peroxisomal disorders are now linked to inherited peroxisomal enzyme abnormalities. Peroxisomal enzyme activities are also altered during pathophysiological conditions through various endogenously produced bio-molecules such as nitric oxide (NO).

Nitric oxide promotes mitogen-induced dna synthesis in human dermal fibroblasts through cGMP.

1. Nitric oxide (NO) is a free radical with multiple functions in cellular pathophysiology. Nitric oxide has been proven to play an important role in wound healing; however, the mechanisms by which NO may promote wound healing are not clearly understood.

A new era for preventive genetic programs in the Arabian Peninsula.

In the Arabian Peninsula, high percentages of consanguineous marriages and the tribal nature of marriages have resulted in high incidence of genetically based disorders. The successful management of these disorders incurs a high financial cost, which is a great burden on the health care system. The practical solution to this problem is through prevention.

A simple, rapid test for the differential diagnosis of glycogen storage disease type 3.

Background: Type 3 glycogen storage disease is an inborn error of metabolism in young infants that often requires extensive workup. However, this disease manifests with few symptoms other than hepatosplenomegaly. At adolescence, this disease may cause myopathy and cardiomyopathy.