ABSTRACT
The new allele, HLA-A*30:81, differs from A*30:01:01 by one nucleotide substitution at codon 272 (CTGâATG).
Subject(s)
Alleles , HLA-A Antigens/genetics , Female , Humans , Male , Sequence Analysis, DNAABSTRACT
CONTEXT: Pseudohypoparathyroidism (PHP) is defined as resistance toward parathyroid hormones. PHP and pseudopseudohypoparathyroidism (PPHP) are rare disorders resulting from genetic and epigenetic aberrations within or upstream of the GNAS locus. This study investigated the clinical characteristics and performed a molecular analysis of PHP and PPHP. METHODS: A total of 12 patients with (P)PHP from 11 unrelated families (4 with PHP-Ia, 6 with PHP-Ib, and 2 with PPHP) were characterized using both clinical and molecular methods. Clinical features included the presenting symptoms, Albright hereditary osteodystrophy features, and resistance to hormones. Comprehensive analysis of the GNAS and STX16 loci was undertaken to investigate the molecular defects underlying (P)PHP. RESULTS: All PHP-Ib patients displayed hypocalcemic symptoms. All PHP-Ia patients showed resistance toward TSH, in addition to PTH. In most patients with PHP, when the diagnosis of PHP was first established, hypocalcemia and hyperphosphatemia were associated with a significant increase in serum PTH levels. One patient with PHP-Ia was diagnosed with growth hormone deficiency and showed a good response to human recombinant growth hormone therapy. 6 patients with PHP-Ia and PPHP showed 5 different mutations in the GNAS gene. 5 patients with PHP-Ib displayed a loss of differentially methylated region (DMR) imprints of the maternal GNAS. One PHP-Ib patient showed a de novo microdeletion in STX16 and a loss of methylation of exon A/B on the maternal allele. No patients revealed paternal disomy among 4 patients with PHP-Ib. CONCLUSIONS: Identification of the molecular causes of PHP and PPHP explains their distinctive clinical features and enables confirmation of the diagnosis and exact genetic counseling.
Subject(s)
Pseudohypoparathyroidism/blood , Pseudohypoparathyroidism/genetics , Pseudopseudohypoparathyroidism/blood , Pseudopseudohypoparathyroidism/genetics , Adult , Aging , Asian People , Child , Child, Preschool , Chromogranins , DNA/genetics , DNA Methylation , DNA Mutational Analysis , Exons , Female , GTP-Binding Protein alpha Subunits, Gs/genetics , Gene Deletion , Growth , Humans , Male , Microsatellite Repeats , Polymerase Chain Reaction , Syntaxin 16/geneticsABSTRACT
The new allele, HLA-C*03:04:36, differs from C*03:04:01:01 by one nucleotide substitution at codon 207 (GGCâGGT).
Subject(s)
Alleles , HLA-C Antigens/genetics , Histocompatibility Testing , Sequence Analysis, DNA , Base Sequence , Humans , Molecular Sequence Data , Sequence AlignmentABSTRACT
[reaction: see text]. We have demonstrated that a dicobalt octacarbonyl catalyzed double [2 + 2 + 1] carbonylative cycloaddition reaction of triyne can be carried out to yield a novel 5.5.5.6 tetracyclic di-enone system.