A disintegrin and metalloprotease 17 (ADAM17) is the major sheddase that processes more than 80 substrates, including tumour necrosis factor-α (TNFα). The homozygous genetic deficiency of ADAM17 causing a complete loss of ADAM17 expression was reported to be linked to neonatal inflammatory skin and bowel disease 1 (NISBD1). Here we report for the first time, a family with NISBD1 caused by functionally confirmed compound heterozygous missense variants of ADAM17, namely c.1699T>C (p.Cys567Arg) and c.1799G>A (p.Cys600Tyr). Both variants were detected in two siblings with clinical features of NISBD1, such as erythroderma with exudate in whole body, recurrent skin infection and sepsis and prolonged diarrhoea. In a cell-based assay using Adam10/17 double-knockout mouse embryonic fibroblasts (Adam10/17−/− mEFs) exogenously expressing each of these mutants, phorbol 12-myristate 13-acetate-stimulated shedding was strongly reduced compared with wild-type ADAM17. Thus, in vitro functional assays demonstrated that both missense variants cause the loss-of-function of ADAM17, resulting in the development of NISBD1. Our study further expands the spectrum of genetic pathology underlying ADAM17 in NISBD1 and establishes functional assay systems for its missense variants.
The purpose of this study was to clarify the effects of individual infection control measures and physical distancing on pediatric medical care in a local prefecture in Japan, where the incidence of coronavirus disease (COVID-19) in pediatric patients was extremely low. We extracted data from hospital records on the number of outpatients, inpatients, infectious disease consultations, and consultations for representative pediatric diseases. We compared attendance in 2017–2019, before the COVID-19 pandemic, with 2020, when COVID-19 spread to Japan. There were no COVID-19 patients in the pediatric department during the study period. The total number outpatient visits decreased by 24.4%, and the number of hospital admissions, excluding neonatal care unit admissions, decreased by approximately 35%. There was a marked reduction in the number of hospitalizations for infectious diseases such as influenza (−74.8%) and respiratory syncytial virus infection (−93.5%), and the number of hospitalizations for bronchitis/pneumonia, Kawasaki disease, and bronchial asthma decreased. In contrast, the number of clinical psychological interventions and cases reported to the child guidance center increased. In the context of pandemic infectious diseases, it is important to control the spread of problematic infectious diseases by individual infection control measures and physical distancing. However, it is necessary to maintain social life as much as possible for the mental health and physical development of children.
Key Clinical MessageWe reported a case of Barber-Say syndrome (BSS) in a Japanese newborn. Distinctive features of BSS were found; macrostomia, gingival dysplasia, cup-shaped low-set ears, wrinkling redundant skin, and hypertrichosis. Fundus showed subretinal drusenoid deposits, a novel finding of BSS. Genetic analysis is underway using next-generation genome sequencing and microarray analysis.
CHARGE syndrome is a rare autosomal dominant developmental disorder involving multiple organs. CHD7 is a major causative gene of CHARGE syndrome. We performed targeted-exome sequencing using a next-generation sequencer for molecular diagnosis of a 4-month-old male patient who was clinically suspected to have CHARGE syndrome, and report a novel monoallelic mutation in CHD7, NM_017780.3(CHD7_v001):c.2966del causing a reading frameshift [p.(Cys989Serfs*3)].
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