OBJECTIVETo analyze the genetic characteristics and molecular mechanism of Chinese patients with Rett syndrome (RTT) and assess the recurrent risk in order to provide genetic counseling for the family with RTT patient.

METHODSMethyl-CpG-binding protein 2 (MECP2) gene mutation analysis were performed on 405 Chinese RTT cases and 292 mothers of the patients with MECP2 mutations with polymerase chain reaction (PCR), direct sequencing and multiplex ligation-dependent probe amplification (MLPA). Then cyclin-dependent kinase-like 5 (CDKL5) and forkhead box protein G1 (FOXG1) genes mutation analysis were performed on the patients without MECP2 mutation. Parental origin of mutated MECP2 gene was detected with allele specific PCR analysis. Based on the difference methylation in CpG island of the first exon of human androgen-receptor gene on active and inactive X-chromosomes, methylation sensitive restriction endonuclease digestion was used to analyze the X-chromosome inactive (XCI) patterns.

RESULTSMECP2 gene mutation was found in 86.9% RTT cases. CDKL5 gene mutation was found in only 3 cases with early-onset seizures variant. No FOXG1 mutation was found. There were 94.4% MECP2 mutations of paternal origin,and point mutations were common. However, microdeletions were common in maternal origin mutation. MECP2 gene mutation was found in only 1 (0.34%,1/292) mother with normal phenotype and non-random XCI pattern. Her daughter was a RTT patient with preserved speech variant, and her XCI pattern was random.

CONCLUSIONMECP2 is the main pathogenic gene in RTT. CDKL5 gene should be screened in patients with early-onset seizures variant without MECP2 gene mutation. The majority of RTT patients had paternally derived de novo MECP2 gene mutation, which may explain the high female to male ratio in RTT. Only 0.34% mothers carried the pathogenic mutation, indicating a lower recurrent risk for RTT families. The XCI may modulate the phenotype of RTT, so MECP2 gene mutation screening in the mothers is important for genetic counseling.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Child ; Child, Preschool ; Female ; Genetic Counseling ; methods ; Genetic Predisposition to Disease ; Humans ; Methyl-CpG-Binding Protein 2 ; genetics ; Prenatal Diagnosis ; methods ; Rett Syndrome ; genetics ; Young Adult

Objective:To summarize the etiology, laboratory examinations and clinical features of rhabdomyolysis(RM)in children.Methods:The clinical data of children with RM admitted to the pediatric general ward at Third Hospital of Peking University from January 1st, 2010 to March 31st, 2021 were collected.The clinical characteristics, etiology distribution, laboratory examinations, treatments and prognosis of the children were analyzed.Results:A total of 24 children were included with 16 males and 8 females.The age ranged from 4 to 15 years old, with median age was 13years old.The etiology was exertional diseases in 14 cases(58.3%), non-exertional diseases in ten cases (41.7%, 7 cases of infection and 3 cases of other causes). The average age of exertional RM was(13.50±1.83)years, and that of non-exertional RM was(8.60±3.72)years.There was significant difference( t=3.848, P=0.002). The main clinical symptoms were muscle soreness, abnormal urine color and muscle weakness.Serum creatine kinase(CK)and serum myoglobin were significantly increased.The proportion of CK value moderate to severe increased of exercise RM children was significantly higher than that of non-exertional RM children( P=0.009). All children were treated with hydration and alkalization.Except for one case who died of critical primary disease, the other 23 children had good treatment response, and no rhabdomyolysis was found during the follow-up. Conclusion:The main causes of rhabdomyolysis in children are exercise and infection.Exertional RM is common in elder children.The increasing of CK level caused by exertional RM is more obvious.Active hydration and alkalization measures could avoid the occurrence of acute kidney injury.Most children with RM have good prognosis.

Objective:To analyze the etiology and clinical characteristics of hospitalized children with fever and cervical lymphadenopathy in general hospital, so as to provide evidence for clinical diagnosis and treatment.Methods:Fifty-six children with fever and cervical lymphadenopathy in the pediatric ward at the Peking University Third Hospital from January 1, 2016 to December 31, 2020 were analyzed retrospectively.They were divided into<6 years old group( n=33) and ≥6 years old group( n=23) according to their ages.The differences of etiological composition among different age groups were analyzed.According to the causes of disease, the cases were divided into infectious disease group and non-infectious disease group.The dynamic changes of etiological composition year by year were analyzed, and the laboratory examination and treatment of children were summarized. Results:Among the 56 cases, 53 cases were confirmed, including 17 cases(30.36%)of acute suppurative lymphadenitis, 13 cases(23.21%)of Kawasaki disease, 13 cases(23.21%)of infectious mononucleosis, seven cases(12.50%)of respiratory tract infection and three cases(5.36%)of histiocytic necrotizing lymphadenitis.As for Kawasaki disease, there were significantly more children in the <6 years old group than that in the ≥ 6 years old group( P=0.005). During the past 5 years, the proportion of infectious diseases have decreased year by year, and the proportion of non-infectious diseases have increased year by year.The difference was statistically significant( χ2=11.443, P=0.022). The levels of leukocyte, neutrophil and quick C-reactive protein in children with non-infectious diseases were higher than those in infectious disease group.The differences were statistically significant(all P<0.05). Among the 56 children, 54 cases(96.4%)were treated with antibiotics.There was no significant difference in the usage rate of antibiotics between the infectious disease group and the non-infectious disease group( χ2=0.019, P=0.890). Conclusion:The main diseases of fever with cervical lymphadenopathy in pediatric inpatients in general hospital are acute suppurative lymphadenitis, Kawasaki disease and infectious mononucleosis, respectively.During the past 5 years, the proportion of non-infectious diseases has increased year by year, but the usage rate of antibiotics has not declined.Clinical attention should be paid to the rational use of antibiotics.