Mosaicism of a novel variant in the ANKRD11 gene in a child with a mild KBG phenotype:A case report

BACKGROUND KBG syndrome is likely underdiagnosed because of mild and non-specific features in some affected patients especially before the upper permanent central incisors eruption at about the age of 7-8 years.Somatic mosaicisms are usually recognized in the parents only after a typically affected son is diagnosed with KBG syndrome.We describe for the first time the mosaicism of a novel variant in a child with a mild KBG phenotype.CASE SUMMARY Our patient presented at 24 mo of age with short stature,hand abnormalities,facial dysmorphism and mild developmental delay.Pituitary hypoplasia and central hypothyroidism were also detected.By next generation sequencing(NGS)analysis we found a novel deletion in the ANKRD11 gene(c.4880_4893del.),that can be classified as likely pathogenic for the syndrome,with the percentage of mutated allele of 36%.We considered this finding as causative of the mild and non-specific phenotype for KBG syndrome in our patient,as previously reported in adults.A heterozygous variant in HESX1 gene,classified as variant of uncertain significance,but suspected of causing pituitary hypoplasia and hormonal deficiency,was also found.The patient started levothyroxine and growth hormone treatment.CONCLUSION The increased use of NGS analysis may expand the phenotypic spectrum of KBG syndrome because it allows genetic diagnosis of somatic mosaicisms also in children.

Ovalicin attenuates atopic dermatitis symptoms by inhibiting IL-31 signaling and intracellular calcium influx

Atopic dermatitis(AD)is a common skin disorder difficult to be treated with medication.This study investigated the potential of ovalicin extracted from Cordyceps militaris for the treatment of AD using in vitro and in vivo models.We found that,in canine macrophage cell line DH82,lipopolysaccharide(LPS)upregulated the expression of genes associated with inflammation and pruritic responses through activating calcium and interleukin-31(IL-31)signaling,and the upregulation could be suppressed by ovalicin,with an effect significantly stronger than dexamethasone.Ovalicin also reduced the expression of IL-31 downstream genes,including JAK2(Janus kinase 2),TRPV1(transient receptor potential vanilloid receptor-1),and HRH2(histamine receptor H2).Ovalicin significantly alleviated the allergic symptoms in the AD mouse model.Histologically,the number of macrophages and mast cells infiltrated in the dermis was significantly reduced by ovalicin treatment.In the skin tissue of AD mice,reduction of IL-31 receptor was observed in the ovalicin treated group compared to the group without ovalicin treatment.To our knowledge,this is the first study to elucidate the anti-atopic mechanism of ovalicin,which could be an alternative to steroidal drugs commonly used for AD treatment.

皮肤淋巴细胞增生性疾病患者发生人疱疹病毒8感染

Objective: To investigate the prevalence of human herpesvirus 8 (HHV-8; Kaposi sarcoma-associated herpes-virus) infection in patients with lymphoproliferative skin diseases such as large plaque parapsoriasis (LPP) and mycosis fungoides compared with inflammatory cutaneous conditions or healthy control subjects. Design: A survey study was undertaken in 123 subjects with various clini cal conditions. Setting: All patients had been seen in the Dermatology Departmen t of the San Gallicano Dermatology Institute, Rome, Italy, in the last 2 years. Patients: Forty-five patientswith inflammatory or autoimmune cutaneous diseases , 50 healthy control subjects, 10 patients with LPP, 12 patients with mycosis fu ngoides, and 6 patients with classic Kaposi sarcoma were included in the study. Main Outcome Measures: The prevalence of HHV-8 infectionwas investigated with s erologic studies using the gold standard assay based on body cavity-based B-cell lymphoma-1 cells latently infected with HHV-8. The presence of HHV-8 conserved sequence, corresponding to open reading frame 26, was also assessed in the peripheral blood and lesion tissue samples from patients with lymphoproliferative cutaneous diseases with nested polymerase chain reaction. The presence and distribution of cell types infected with HHV-8 in the lesion tissues was determined with immunohistochemical staining with the monoclonal antibody directed against the latent nuclear antigen-1 of HHV-8 encoded by open reading frame 73. Results: In healthy control subjects and patients with inflammatory skin diseases, 13.9%were found to have antibody against HHV-8, consistent with the seroprevalence population in Italy. A highly significant association of HHV-8 infection and LPPwas found (100%) compared with mycosis fungoides (25%). The peripheral blood mononuclear cells in 8 of 10 patients with LPP were found to harbor viral sequences at nested polymerase chain reaction, whereas none of them had a detectable serum viral load. All LPP lesion tissue samples were positive for HHV-8-encoded open reading frame 26, and the presence of HHV-8-infected cells was confirmed by immunohistochemistry profiles performed on paraffin-embedded tissues from 4 of 10 patients. The positive cell types included endothelial cells and the infiltrating dermal lymphocytes, characteristic hallmarks of LPP. Analysis of T cell receptor γchain rearrangements in lesion tissue from our patients confirme d the lack of a significant association between T-cell clonality and LPP. Concl usion: These data suggest that HHV-8 may play a role in the onset of LPP, a dis ease whose cause and evolution are still undefined and which has often been cons idered the early stage of mycosis fungoides.

Septic Shock after Intravesical BCG Instillation—A Case Report

Bacillus Calmette-Guérin (BCG) is a live attenuated form of Mycobacterium bovis, initially used in medicine as a vaccination agent only. The discovery of its antineoplastic effects in bladder cancer has led to the widespread recognition of BCG intravesical instillation as a therapeutic option. Although sepsis following BCG intravesical instillation is rare, it is nonetheless a dreadful and potentially fatal complication. Therapy usually relies on antituberculous therapy and steroids, alongside with intensive care unit admission. The authors report a case of a 67-year-old male patient who developed septic shock with multiple organ dysfunction after intravesical BCG instillation and review the currently available knowledge concerning the risk factors, diagnosis, management and prevention of BCG sepsis.

A rare case of omental extra-gastrointestinal stromal tumor showing two coexisting mutations on exon 14 of the PDGFRA gene

Introduction Gastrointestinal stromal tumors(GISTs)are neoplasms arising from mesenchymal cells localized into the muscularis propria of the gastrointestinal(GI)tract[1];5%of GISTs are extra-GISTs(EGISTs),as they differently originate from adipose tissue adjacent to the GI tract(omentum and mesentery)or from the pancreas[2].So far,both GISTs and EGISTs have been managed indistinctively by combining surgery,histopathological distinctive features,imaging,and molecular analysis.Moreover.