RESUMEN
We reported a case of microcephaly-capillary malformation(MIC-CAP)caused by STAMBP gene variant,in order to improve the clinical diagnosis and treatment.The patient is a 3-month-old male with recurrent convulsions and the main clinical manifestations are multiple forms of seizures,microcephaly,multiple small capillary malformations in the skin,and generalized hypotonia.The genetic test showed that a heterozygous variant in the STAMBP gene was present in the child.Both parents were heterozygous carriers.He was administrated various anti-seizure medications and ketogenic diet,but still had frequent seizures.He then underwent corpus callosotomy,and was followed up until he was 4 years and 10 months old.The post operational outcome was grade IV on Engel's classification.Based on the clinical data of 22 patients in literature,in addition to severe psychomotor retardation,microcephaly,and cutaneous capillary malformations,early-onset drug-refractory epilepsy is also a major feature of MIC-CAP syndrome,which is clinically rare and has a poor prognosis;Callosotomy may help to reduce seizures in the short term.However,the long-term outcome is poor.STAMBP gene is the main responsible gene for this syndrome.
RESUMEN
Objective To observe the effect of interferon (IFN) λ1 on the function of peripheral blood mononuclear cell (PBMC) derived dendritic cells (DC) in adolescents with chronic hepatitis B virus (HBV) infection.Methods A total of 34 adolescent patients with chronic HBV infection including 16 cases in immune clearance phase and 18 cases in immune tolerant phase,and 10 healthy youths were enrolled in the study.PBMC from all samples were isolated and then cultured according to the following 3 groups.IFN-λ1 group:cultured with IFN-λ1 only; normal group:cultured with recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) and recombinant human interleukin-4 (rhIL-4); combination group:cultured with IFN-λ1,rhGM-CSF and rhIL-4.The shape of DC was observed and the phenotypic patterns of CD83,CD80,CD86 and human leucocyte antigen (HLA)-DR were characterized by flow cytometry.The levels of interleukin 12 (IL-12) and IFN-γ in the supernatant produced by DC were analyzed with enzyme-linked immunosorbent assay (ELISA).Independent-samples t test was used to compare means between two groups and one-way ANOVA was used to compare means among multiple groups.Results In the IFN-λ1 group,the shape of adherent cells showed no change after 7 days of culture.In the normal group and combination group,typical morphology of mature state DC was observed.The expressions of phenotypic patterns of CD83,CD80,CD86 and HLA-DR in DC from immune tolerant phase patients were lower than those from healthy control youths and immune clearance phase patients (F=14.82-46.32,all P＜0.01).Co-stimuation of IFN-λ1 with rhGM-CSF and rhIL-4 up-regulated the expressions of phenotypic patterns on DC.Among patients both in immune tolerant phase and immune clearance phase,the expressions of CD83,CD80,CD86 and HLA-DR in the combination group were higher than those in normal group (t=3.16-5.69,all P＜0.01).In the normal group,the levels of IL-12 and IFN-γ in culture supernatants from healthy aldolescents were (287.25 ± 19.78) pg/mL and (56.38 ± 15.27)pg/mL,respectively; those from patients in immune tolerant phase were (198.42±22.28) pg/mL and (29.36±8.45) pg/mL,respectively; those from patients in immune clearance phase were (256.12±18.43) pg/mL and (38.38±9.72) pg/mL,respectively (F=69.22 for IL-12,F=20.29 for IFN-γ,both P＜0.01).IFN-λ1 combined with rhGM-CSF and rhIL-4 significantly up-regulated the secretion of IL-12 and IFN-γ by matured DC from patients both in immune tolerant phase and immune clearance phase (t=4.69-8.55,all P＜0.01).Conclusions In adolescent patients with chronic HBV infection,the DC function is markedly impaired in those in immune tolerant phase,compared with patients in immune clearance phase and healthy youths.IFN-λ1 can promote the maturation and phenotypic pattern expression of PBMC derived DC in adolescents with chronic HBV infection both in immune tolerant phase and immune clearance phase.