Objective To study the NR5A1 gene mutation in patients with idiopathic hypogonadotropic hypogonadism(IHH), and to find the new mutation point.Methods Sixty-one IHH patients and 100 normal control subjects were collected and genomic DNA was extracted from blood samples.These patients were with normal karyotype and no abnormality was discovered in magnetic resonance imaging (MRI) scan of the pituitary.Other endocrine diseases were also excluded.The 2-7 exons and splice-sites of NR5A1 gene were amplified with polymerase chain reaction.DNA of the coding sequence and splice-sites of NR5A 1 were sequenced by double deoxidizing terminal end sequencing method in 61 IHH and 100 normal control subjects.The results of sequencing were compared with their corresponding sequence data.61 IHH kindreds were investigated and the clinical data of these patients were collected.Finally, the phenotype and genotype positive cases were analyzed.Results Six patients carried NR5A1 gene mutational sites in 61 cases of IHH.Analysis of sequencing results from 100 age and ethnicity matched control subjects did not show any of these novel changes.Conclusions One mutation in NR5A1 gene may affect protein structure and function, which should be considered in male IHH patients with normal karyotype and without insufficiency of adrenal function.

Objective To analyze the clinical and genetic features of immunodeficiency,centromeric instability,and facial anomalies (ICF) syndrome with a case report and literature review.Methods The clinical data and genetic test of a girl diagnosed with ICF syndrome in the Department of Nephrology and Immunology in Qingdao Women and Children's Hospital in December 2016 were extracted and analyzed."ICF syndrome" "immunodeficiency,centromeric instability and facial anomalies syndrome" "ICF syndrome and DNMT3B" were used as key words to search Chinese databases and Pubmed for literature until March 2018,and the literature was reviewed.Results A female patient aged 22 months old with ocular hypertelorism and low-set ears was admitted due to recurrent infection over one year.Laboratory tests showed humoral immune deficiency with IgG＜ 1.34 g/L,IgA＜0.060 g/L,and IgM＜0.179 g/L,but normal cellular immunity (total T lymphocyte 0.503,hepler T lymphocyte 0.328,cytotoxic T lymphocyte 0.166,natural killer cell 0.184,total B lymphocyte 0.276).Whole-exome sequencing revealed a de novo heterozygous splice site mutation c.922-2A＞G in intron 8,and a de novo heterozygous missense mutation c.2477G＞A in exon 23 of DNMT3B gene.Chromosome karyotype analysis showed 46,XX,with 64 out of 100 karyotypes showing centromere instability in chromosome 1.Five papers were found which were all in English,with total of 29 patients.Forty-three mutations were reported,including 34 missense,2 deletion,1 insertion,6 splice site mutations.Eleven patients had complex heterozygosis mutations.All patients had centromere instability,humoral immune deficiency and facial dysplasia which were mainly ocular hypertelorism and low-set ears.Most patients had language and motor development delay,and a few were combined with mental retardation.Conclusions ICF syndrome is a rare autosomal recessive primary immunodeficiency with classic clinical triad manifestations.De novo mutation of DNMT3B gene is one of etiologies according to genetic test.

Objective:To study the effect of continuous subcutaneous insulin infusion (CSII) in the long-term treatment of type 1 diabetes mellitus (T1DM) children, to analyze the factors influencing the efficacy, and to provide theoretical guidance for the application of CSII in long-term therapy and follow-up management.Method:A total of 60 T1DM children who were under 18 years old, lived in Qingdao for a long time, had CSII for more than 6 months, and visited the Outpatient Department of Endocrinology of Qingdao Women and Children′s Hospital for a long term from January 2019 to June 2019 were followed up with questionnaires to understand their general condition and treatment-related data.Result:After the CSII therapy, the hemoglobin A1c (HbA1c) of T1DM children significantly decreased from (9.58±2.08)% to (7.12±1.11)% ( t=7.315, P<0.05), the daily insulin dosage per unit weight significantly declined from 0.91(0.86, 0.94) IU to 0.80 (0.66, 0.88) IU ( Z=-5.514, P<0.05), and the frequency of both hypoglycemia and ketoacidosis was significantly reduced.Diet control, daily exercise time, the visit frequency and the self-monitoring frequency of blood glucose affected the curative effect of CSII therapy (all P<0.05). Conclusion:CSII therapy can effectively control the blood glucose of children with T1DM in Qingdao area, significantly lower HbA1c, and reduce the insulin dosage and the incidence of hypoglycemia and ketoacidosis.Good diet control, regular exercise, regular follow-up and a high frequency of blood glucose monitoring are associated with better glycemic control.