ABSTRACT
OBJECTIVE@#To explore the clinical phenotype and genetic etiology of a child with early-onset severe obesity.@*METHODS@#A child who presented at the Department of Endocrinology, Hangzhou Children's Hospital on August 5, 2020 was selected as the study subject. Clinical data of the child were reviewed. Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing (WES) was carried out on the child. Candidate variants were verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#This child was a 2-year-and-9-month girl featuring severe obesity with hyperpigmentation on the neck and armpit skin. WES revealed that she has harbored compound heterozygous variants of the MC4R gene, namely c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp). Sanger sequencing confirmed that they were respectively inherited from her father and mother. The c.831T>A (p.Cys277*) has been recorded by the ClinVar database. Its carrier frequency among normal East Asians was 0.000 4 according to the 1000 Genomes, ExAC, and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as pathogenic. The c.184A>G (p.Asn62Asp) has not been recorded in the ClinVar, 1000 Genomes, ExAC and gnomAD databases. Prediction using IFT and PolyPhen-2 online software suggested it to be deleterious. Based on the guidelines from the ACMG, it was determined as likely pathogenic.@*CONCLUSION@#The c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp) compound heterozygous variants of the MC4R gene probably underlay the early-onset severe obesity in this child. Above finding has further expanded the spectrum of MC4R gene variants and provided a reference for the diagnosis and genetic counseling for this family.
Subject(s)
Female , Humans , Child, Preschool , Computational Biology , East Asian People , Genetic Counseling , Genomics , Mutation , Obesity, Morbid/genetics , Pediatric Obesity/geneticsABSTRACT
A 13-year-old male patient presented with skin abnormalities for more than 10 years and slow growth in body height for more than 5 years. Since the age of 6 months, erythema and scales had occurred on the extremities, and gradually spread to the trunk and face; brown pigmentation and punctate depigmentation appeared after subsidance of the erythema and scales, accompanied by dental caries, thickened palms and soles, nail thickening and peeling. Since the age of 6 years, the patient had presented with slow growth in body height, gonadal dysgenesis, sparse eyebrows and eyelashes, flat cheekbones and lameness in walking. In the past 10 years, neutrophil count had been found to be continuously lower than the normal reference value. Blood routine examination showed a neutrophil count of 1.1 × 10 9/L and a neutrophil proportion of 0.345; serum level of testosterone in the patient (< 0.087 nmol/L) was lower than normal levels. DNA was extracted from the peripheral blood of the patient and his parents, and gene mutation analysis was carried out by using whole-exome sequencing technology. Genetic testing showed compound heterozygous mutations in the USB1 gene of the patient, including the c.450-2A>G mutation inherited from his mother and the c.335de1G mutation inherited from his father, and the c.335de1G mutation had not been reported in China and other countries.
ABSTRACT
Objective To investigate the change of T-lymphocyte subgroup in children with infectious mononucleosis (IM).Methods Sixty young children with IM caused by Epstein-Barr virus (EBV) were recruited for this study in Jiaxing First Hospital from Jan 2005 to Dec 2010.Thirty-six normal children were chosen as control group.Both of the two groups were detected blood test,blood smear,T-lymphocyte subgroup ( including CD3,CD4,CD8,CD4/CD8 ),liver and kidney function test,IgM antibodies of EBV,cytomegalovirus,adenovirus,and hepatitis virus.Results Compared with the control group (53.58％ ± 5.97％,31.22％±8.72％ ),the ratio of CD3 (81.55％ ±9.04％ ) and CD8(58.13％ ± 13.35％ ) were significantly higher in IM group( P ＜0.05 ).And the ratio of CD4 ( 18.19％ ± 7.61％ ) and CD4/CD8 (0.37 ± 0.33) were significantly lower in IM group,compared with the control group (36.98％ ± 5.32％,1.98 ± 0.41 )(P ＜ 0.05 ).While the leukocyte count,the ratio of abnormal leukomonocyte,and alanine transaminase had no correlation with the decrease of CD4/CD8 ( P ＞ 0.05 ).Conclusion Children with IM caused by EBV have bad immunocompetence,and we can treat them with immunotherapy early.
ABSTRACT
Objective To study the etiology of comumunity acquired pneumonia (CAP) in children of Jiaxing city and provide the basis for the clinical diagnosis and treatment.Methods An etiological study was performed on 800 young children with CAP in Jinxing First Hospital from Jan 2008 to Dec 2010.Sputum samples were collected for isolating bacteria and checking the antigen of respiratory syncytial virus ( RSV),adenovirus ( ADV),influenza virus (IV) and parainfluenza virus ( PIV ).IgM antibodies of mycoplasma pneumoniae (MP),ADV,W and PIV paired serum samples were detected.The 202 cases with positive etiology were divided into three groups:bacteria group ( 109 cases),virus group (54 cases) and MP group (39 cases).The leukocyte,C-reactive protein (CRP) and procalcitonin (PCT) were detected.Results The etiology of CAP was identified in 202 (25.25％) children of all the 800 cases,the distribution of causal agents was as follows:Streptococcus pneumoniae in 46 cases (22.77％,46/202 ),Haemophilus influenzae in 32 cases (15.84％,32/202),Staphylococcus in 5 cases (2.48％,5/202),Klebsiella pneumoniae in 8 cases (3.96％,8/202),Escherichia coli in 12 cases (5.94％,12/202),MP in 39 cases ( 19.31％,39/202),RSV in 48 cases (23.76％,48/202),ADV in 1 case (0.50％,1/202),IV in 3 cases ( 1.49％,3/202),and PIV in 2 cases ( 0.99％,2/202 ),Streptococcus pneumoniae and RSV mixed infection in 3 cases ( 1.49％,.3/202),Streptococcus pneumoniae and MP mixed infection in 3 cases ( 1.49％,3/202).RSV infection occured mainly in infants less than 1-year-old,Streptococcus pneumoniae oceured in all ages but was mostly in 1 ～ 3years,Haemophilus influenzae infection occured mainly in infants less than 3-year-old,MP infection occured mainly in infants more than six years.The PCT levels of the three groups were (7.78 ±6.14) ng/ml,(0.39 ±0.56) ng/ml,and (0.20 ±0.34) ng/ml,respectively.There were significant differences among the three groups ( P ＜ 0.05 ).Conclusion RSV infection occurs mainly in infants of age less than 1 year,Streptococcus pneumoniae and Haemophilus influenzae infection occur mainly in infants of age 1 ～3 years,while MP is the leading cause of pneumonia in children of age more than 6 years in Jiaxing city.We can decide pathogen on ages,clinical manifestation and PCT level to guide the rational use of drugs.