Environmental influences on familial discordance of phenotype in people with homocystinuria: a case report

<p>Abstract</p> <p>Introduction</p> <p>Non-heritable factors may have an influence on the clinical expression of monogenic inherited metabolic diseases.</p> <p>Case presentation</p> <p>This is a case report of a man whose mother had been diagnosed late in childhood with pyridoxine responsive homocystinuria with lens dislocation and neurodevelopmental delay. These severe complications were not observed in her son who was pyridoxine unresponsive but who had been treated appropriately since early infancy.</p> <p>Conclusion</p> <p>The phenotype of people with homocystinuria can be discordant within a family, with variability in metabolic and clinical expression depending upon both the genotype and therapeutic interventions. Offspring of people with homocystinuria should be screened in early infancy and, if positive, treated appropriately whether they have pyridoxine responsive or unresponsive disease.</p

PTPN22 R620W polymorphism in the ANCA-associated vasculitides

Objectives. PTPN22 is involved in T-cell activation and its R620W single-nucleotide polymorphism ( SNP) has been shown to predispose to different autoimmune diseases. The aims of this study were to investigate the role of the PTPN22 R620W SNP in conferring susceptibility to the ANCA-associated vasculitides (AAVs), and to explore potential associations between the PTPN22 genotype and the disease manifestations. Methods. PTPN22 R620W SNP was genotyped in a cohort of 344 AAV patients [143 with granulomatosis with polyangiitis (Wegener's) (GPA), 102 with microscopic polyangiitis (MPA) and 99 with Churg-Strauss syndrome (CSS)] and in 945 healthy controls. Results. The frequency of the minor allele (620W) was significantly higher in GPA patients than in controls [P = 0.005, chi(2) = 7.858, odds ratio (OR) = 1.91], while no statistically significant association was found with MPA or CSS. Among GPA patients, the 620W allele was particularly enriched in ANCA-positive patients as compared with controls (P = 0.00012, chi(2) = 14.73, OR = 2.31); a particularly marked association was also found with ENT involvement (P = 0.0071, chi(2) = 7.258, OR = 1.98), lung involvement (P = 0.0060, chi(2) = 7.541, OR = 2.07) and skin manifestations of all kinds (P = 0.000047, chi(2) = 16.567, OR = 3.73). Conclusion. The PTPN22 620W allele confers susceptibility to the development of GPA (but not of MPA or CSS), and particularly of its ANCA-positive subset