RESUMO
Silver-Russell syndrome (SRS) is a congenital disorder characterized by prenatal and postnatal growth failure and craniofacial features. Hypomethylation of the H19/IGF2:IG-differential methylated region (H19LOM) is observed in 50% of SRS patients, and 15% of SRS patients with H19LOM had multilocus imprinting disturbance (MLID). Schimke immuno-osseous dysplasia (SIOD), characterized by spondyloepiphyseal dysplasia and nephropathy, is an autosomal recessive disorder caused by mutations in SMARCAL1 on chromosome 2. We report a patient with typical SRS-related features, spondyloepiphyseal dysplasia, and severe nephropathy. Molecular analyses showed H19LOM, paternal uniparental isodisomy of chromosome 2 (iUPD(2)pat), and a paternally inherited homozygous frameshift variant in SMARCAL1. Genome-wide methylation analysis showed MLID in this patient, although it showed no MLID in another patient with SIOD without SRS phenotype. These results suggest that iUPD(2)pat unmasked the recessive mutation in SMARCAL1 and that the SMARCAL1 gene mutation may have no direct effect on the patient's methylation defects.
Assuntos
Arteriosclerose/genética , DNA Helicases/genética , Metilação de DNA/genética , Síndrome Nefrótica/genética , Osteocondrodisplasias/genética , Doenças da Imunodeficiência Primária/genética , Embolia Pulmonar/genética , Síndrome de Silver-Russell/genética , Arteriosclerose/complicações , Arteriosclerose/fisiopatologia , Criança , Pré-Escolar , Cromossomos Humanos Par 2/genética , Feminino , Genoma Humano/genética , Impressão Genômica/genética , Humanos , Recém-Nascido , Masculino , Síndrome Nefrótica/complicações , Síndrome Nefrótica/fisiopatologia , Osteocondrodisplasias/complicações , Osteocondrodisplasias/fisiopatologia , Fenótipo , Doenças da Imunodeficiência Primária/complicações , Doenças da Imunodeficiência Primária/fisiopatologia , Embolia Pulmonar/complicações , Embolia Pulmonar/fisiopatologia , Síndrome de Silver-Russell/complicações , Síndrome de Silver-Russell/fisiopatologia , Dissomia Uniparental/genética , Dissomia Uniparental/fisiopatologiaRESUMO
Plasma exchange is a therapeutic option in refractory Kawasaki disease (KD). However, the effects of other immunosuppressive treatments on plasma exchange therapy have not been studied. We investigated the effect of infliximab on plasma exchange in KD as well as on the outcome in patients with KD. We studied 16 patients with intravenous immunoglobulin-resistant KD who finally underwent plasma exchange. The patients were divided into two groups: patients who received infliximab before plasma exchange (infliximab group) and patients who did not (non-infliximab group). The infliximab group showed a lesser median number of required total plasma exchange sessions (P = .002) and higher change and reduction rates in C-reactive protein before and after the first plasma exchange (both P = .027) than that of the non-infliximab group. Infliximab administered before plasma exchange reduced the number of total plasma exchange sessions and improved the plasma exchange efficacy.