To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations in the HLA-DR/DQ region, common variants in NPHS1-KIRREL2 (rs56117924, P[4.94E-20, odds ratio (OR) [1.90)

Our results suggest that a recently developed therapeutic regimen with cyclosporine considerably improves both the initial remission rate and the long-term renal survival rate of children with idiopathic SRNS.

Joubert syndrome (JS) is rare recessive disorders characterized by the combination of hypoplasia/aplasia of the cerebellar vermis, thickened and elongated superior cerebellar peduncles, and a deep interpeduncular fossa which is defined by neuroimaging and is termed the 'molar tooth sign'. JS is genetically highly heterogeneous, with at least 29 disease genes being involved. To further understand the genetic causes of JS, we performed whole-exome sequencing in 24 newly recruited JS families. Together with six previously reported families, we identified causative mutations in 25 out of 30 (24 + 6) families (83.3%). We identified eight mutated genes in 27 (21 + 6) Japanese families, TMEM67 (7/27, 25.9%) and CEP290 (6/27, 22.2%) were the most commonly mutated. Interestingly, 9 of 12 CEP290 disease alleles were c.6012-12T>A (75.0%), an allele that has not been reported in non-Japanese populations. Therefore c.6012-12T>A is a common allele in the Japanese population. Importantly, one Japanese and one Omani families carried compound biallelic mutations in two distinct genes (TMEM67/RPGRIP1L and TMEM138/BBS1, respectively). BBS1 is the causative gene in Bardet-Biedl syndrome. These concomitant mutations led to severe and/or complex clinical features in the patients, suggesting combined effects of different mutant genes.

No abstract

Although there are many reports on the resistance of Kawasaki disease (KD) to initial intravenous immunoglobulin (IVIg) therapy, risk factors for coronary artery lesions in such cases remain to be established. The objective of this study was to explore when additional therapies should be administered and to identify factors helpful for selecting a therapeutic option. Based on their written clinical records, we performed a retrospective review of KD patients who did not respond to initial IVIg therapy and who therefore then underwent plasma exchange (PE) therapy. This was a case-control study to compare the presence or absence of acute coronary lesions in patients treated by PE for IVIg-unresponsive KD at Yokohama City University Hospital or at Yokohama City University Medical Center. Fifteen of 44 patients had acute coronary artery lesions (CAL) correlating with high levels of white blood cells (WBC) (P = 0.045), D-dimer (P = 0.008), and fibrin/fibrinogen degradation products (P = 0.009) and lower levels of fibrinogen (P = 0.013) prior to PE therapy. There was a strong correlation between pre-PE levels of albumin and D-dimer (Pearson's correlation coefficient of 0.610). Multivariate analyses revealed that the odds ratio for CAL when D-dimer was ≥ 4.5 μg/mL was 25.06 (95% CI, 2.56-244.91, P = 0.006). D-dimer elevation and albumin decline in IVIg-unresponsive KD patients could be risk factors for acute CAL, suggesting the possibility that angitis has spread throughout the arterial system, as far as the coronary artery.

No abstract

Kawasaki disease is a generalized vasculitis of unknown etiology that occurs predominantly in infants and young children. It is very important to prevent its cardiovascular manifestations, especially coronary artery lesions. Early treatment with intravenous immunoglobulin reduces cardiovascular sequelae, but some patients do not respond to this treatment, and they have a high incidence of coronary artery lesions. On the other hand, acute heart failure is rare in Kawasaki disease. We report on the cases of two patients with persistent fever and shock even after intravenous immunoglobulin therapy. In both cases, plasma exchange may have reduced the risk of coronary artery lesions and proved effective against acute heart failure with catecholamine-refractory shock; yet the mechanism of this improvement remains unclear.

No abstract