heparitin-sulfate and Mental-Disorders

Next-generation sequencing (NGS) techniques have already shown their potential in the identification of mutations underlying rare inherited disorders. We report here the application of linkage analysis in combination with targeted DNA capture and NGS to a Norwegian family affected by an undiagnosed mental retardation disorder with an autosomal recessive inheritance pattern. Linkage analysis identified two loci on chromosomes 9 and 17 which were subject to target enrichment by hybridization to a custom microarray. NGS achieved 20-fold or greater sequence coverage of 83% of all protein-coding exons in the target regions. This led to the identification of compound heterozygous mutations in NAGLU, compatible with the diagnosis of Mucopolysaccharidosis IIIB (MPS IIIB or Sanfilippo Syndrome type B). This diagnosis was confirmed by demonstrating elevated levels of heparan sulphate in urine and low activity of α-N-acetyl-glucosaminidase in cultured fibroblasts. Our findings describe a mild form of MPS IIIB and illustrate the diagnostic potential of targeted NGS in Mendelian disease with unknown aetiology.

Topics: Acetylglucosaminidase; Cells, Cultured; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 9; DNA Mutational Analysis; Female; Fibroblasts; Genetic Linkage; Genetic Loci; Genome, Human; Heparitin Sulfate; Humans; Inheritance Patterns; Male; Mental Disorders; Middle Aged; Mucopolysaccharidosis III; Mutation; Norway; Oligonucleotide Array Sequence Analysis; Pedigree

In the past 10 years numerous reports of cases referring to complications and their outcome with heparin-induced thrombocytopenia type II (HIT II) have been published. Clinically these symptoms are manifested as a combination of arterial and venous thromboembolisms. Mostly affected are the vessels of the limbs, the abdomen, kidneys and coronary arteries. We present the most rare initial manifestations of cerebral symptoms with headache, nausea, change of character and generalised convulsion, which have found their origin in sinus vein thrombosis and the treatment with the heparinoid danaparoid.

Topics: Aged; Anticoagulants; Anticonvulsants; Blood Cell Count; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heparin; Heparitin Sulfate; Humans; Male; Mental Disorders; Postoperative Complications; Seizures; Sinus Thrombosis, Intracranial; Thrombocytopenia; Tomography, X-Ray Computed