RESUMEN
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.
Asunto(s)
Arteriosclerosis/genética , ADN Helicasas/genética , Metilación de ADN/genética , Síndrome Nefrótico/genética , Osteocondrodisplasias/genética , Enfermedades de Inmunodeficiencia Primaria/genética , Embolia Pulmonar/genética , Síndrome de Silver-Russell/genética , Arteriosclerosis/complicaciones , Arteriosclerosis/fisiopatología , Niño , Preescolar , Cromosomas Humanos Par 2/genética , Femenino , Genoma Humano/genética , Impresión Genómica/genética , Humanos , Recién Nacido , Masculino , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/fisiopatología , Osteocondrodisplasias/complicaciones , Osteocondrodisplasias/fisiopatología , Fenotipo , Enfermedades de Inmunodeficiencia Primaria/complicaciones , Enfermedades de Inmunodeficiencia Primaria/fisiopatología , Embolia Pulmonar/complicaciones , Embolia Pulmonar/fisiopatología , Síndrome de Silver-Russell/complicaciones , Síndrome de Silver-Russell/fisiopatología , Disomía Uniparental/genética , Disomía Uniparental/fisiopatologíaRESUMEN
Transient receptor potential channel C6 encoded by TRPC6 is involved in slit diaphragm formation in podocytes, and abnormalities of the TRPC6 protein cause various glomerular diseases. The first identified pathogenic variant of TRPC6 was found to cause steroid-resistant nephrotic syndrome that typically developed in adulthood and then slowly led to end-stage renal disease, along with a renal pathology of focal segmental glomerulosclerosis. Here, we report a patient with rapidly progressing infantile nephrotic syndrome and a heterozygous missense TRPC6 variant. The patient, a 2-year-old Japanese boy, developed steroid-resistant nephrotic syndrome at age 11 months. His renal function deteriorated rapidly, and peritoneal dialysis was introduced at age 1 year and 6 months. His renal pathology, obtained at age 1 year and 1 month, was consistent with diffuse mesangial sclerosis (DMS). Clinical exome analysis and custom panel analysis for hereditary renal diseases revealed a reported heterozygous missense variant in TRPC6 (NM_004621.5:c.523C > T:p.Arg175Trp). This is the first report of a patient with a TRPC6-related renal disorder associated with DMS.
Asunto(s)
Enfermedades Renales/genética , Síndrome Nefrótico/genética , Esclerosis/genética , Canal Catiónico TRPC6/genética , Preescolar , Exoma/genética , Predisposición Genética a la Enfermedad , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Glomeruloesclerosis Focal y Segmentaria/diagnóstico por imagen , Glomeruloesclerosis Focal y Segmentaria/genética , Glomeruloesclerosis Focal y Segmentaria/patología , Heterocigoto , Humanos , Lactante , Riñón/diagnóstico por imagen , Riñón/patología , Enfermedades Renales/complicaciones , Enfermedades Renales/diagnóstico por imagen , Enfermedades Renales/patología , Masculino , Mutación Missense/genética , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/diagnóstico por imagen , Síndrome Nefrótico/patología , Podocitos/metabolismo , Podocitos/patología , Esclerosis/complicaciones , Esclerosis/diagnóstico por imagen , Esclerosis/patologíaRESUMEN
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.
