Prevalence of p.G87V and p.Gln298=Variations in Gene Within Middle Eastern Population Living Around Los Angeles.

The gene encodes for lysosomal acid lipase (LAL), which catalyzes the hydrolysis of cholesterol esters and triglycerides. Variations in the gene impair LAL activity, predisposing patients to a rare metabolic disorder called LAL deficiency (LAL-D). The lack of functioning LAL promotes lipid accumulation and subsequent dyslipidemia, which can increase the likelihood of complications in both infants and adults.

Targeting GNE Myopathy: A Dual Prodrug Approach for the Delivery of -Acetylmannosamine 6-Phosphate.

ProTides comprise an important class of prodrugs currently marketed and developed as antiviral and anticancer therapies. The ProTide technology employs phosphate masking groups capable of providing more favorable druglike properties and an intracellular activation mechanism for enzyme-mediated release of a nucleoside monophosphate. Herein, we describe the application of phosphoramidate chemistry to 1,3,4--acetylated -acetylmannosamine (AcManNAc) to deliver ManNAc-6-phosphate (ManNAc-6-P), a critical intermediate in sialic acid biosynthesis.

Non-GNE Quadriceps Sparing Distal Myopathy in an Iranian Jewish Patient.

GNE myopathy is an autosomal-recessive distal myopathy. It is caused by a hypomorphic GNE gene, encoding the rate-limiting enzyme in sialic acid synthesis. This myopathy is prevalent in the Iranian Jewish (IJ) descendants because of a founder mutation GNE: p.

Novel GNE mutations in autosomal recessive hereditary inclusion body myopathy patients.

Hereditary Inclusion Body Myopathy (HIBM, IBM2, MIM:600737) is an autosomal recessive adult onset progressive muscle wasting disorder. It is associated with the degeneration of distal and proximal muscles, while often sparing the quadriceps. The bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE/MNK), encoded by the GNE gene, catalyzes the first two committed, rate-limiting steps in the biosynthesis of N-acetylneunaminic acid (sialic acid).

Serum neural cell adhesion molecule is hyposialylated in hereditary inclusion body myopathy.

Hereditary inclusion body myopathy (HIBM) is a young-adult onset autosomal recessive disorder caused by a hypomorphic rate limiting enzyme of sialic acid biosynthesis. The enzyme is UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, and is encoded by the GNE gene. HIBM causes slowly progressive muscle weakness and atrophy.

Wolman disease (LIPA p.G87V) genotype frequency in people of Iranian-Jewish ancestry.

Wolman disease (WD) is a rare inherited condition caused by lysosomal acid lipase (LAL) deficiency first described in Iranian-Jewish (IJ) children. Newborns with WD are healthy and active, but soon the infant develops symptoms of severe malnutrition in the first few months of life, and often dies before the age of 1 year. Harmful amounts of lipids accumulate in the spleen, liver, bone marrow, intestine, adrenal glands, and lymph nodes.

Novel GNE mutations in hereditary inclusion body myopathy patients of non-Middle Eastern descent.

Autosomal recessive hereditary inclusion body myopathy (HIBM or IBM2) is a progressive adult onset muscle wasting disorder characterized by sparing of the quadriceps. IBM2 is also known as distal myopathy with rimmed vacuoles or nonaka myopathy. IBM2 is associated with mutations in the UDP-GlcNAc 2-Epimerase/ManNAc Kinase gene (GNE).

MTHFR C677T genotype frequency in patients of Middle Eastern descent as determined by real-time PCR and melting curve analysis.

The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) 677C>T polymorphism produces an elevation in plasma homocysteine concentrations when present in the homozygous state. Increased homocysteine levels have been associated with a greater risk for vascular diseases, including cardiovascular disease and ischemic stroke. In this study, we genotyped 42 nucleic acid samples for the C677T allele from our database of Middle Eastern patients as routine validation of the MTHFR 677C>T assay.

Validation of GNE:p.M712T identification by melting curve analysis.

Hereditary inclusion body myopathy/distal myopathy with rimmed vacuoles is an adult onset autosomal recessive muscle-wasting disease common in people of Iranian-Jewish descent, due to the founder allelic variant GNE:p.M712T. High correlation of disease susceptibility with GNE:p.