| Background:Rett syndrome (RTT) is a rare X-linked dominant genetic disease, combine with autism, atypical autism, Asperger’s syndrome, nonspecific broad developmental disorders, all belong to the pervasive developmental disorder (PPD). RTT is predominantly found in females, with an estimated prevalence of approximately one in 10000-15000 female births. Most of them are sporadic cases, only 0.5%～1%cases are familial recurrence. Main of patients have normal mental and sportive development in early ages, suffered disease from 6 months to 18 months, with hand rigid motion, loss of the hand function, and obvious developmental abnormalities. RTT is a common cause of the woman mental retardation. The disease gene responsible for this disorder is methylation CpG binding protein-2 (methyl-CpG-binding protein 2, MECP2) gene, located in the Xq28. The diagnosis of RTT mainly relies on the corresponding clinical criteria. But for clinical doctors who do not know the disease and the children behave differently enough, the misdiagnosis may be done. This study accomplished in the Chengdu Women & Children’s Medical Central Hospital, from April - August in 2014. Clinical analysis, pedigree investigation, karyotype analysis, MECP2 gene amplification sequencing were done in 4 cases of suspected cases. It will improve the understanding of the disease in clinical work.Objectives:1. To investigate the clinical characteristics of suspected cases of RTT in our cohort.2. To investigate the pathogenic role of MECP2 gene mutations in the 4 cases of suspected cases.3. To clarify the mode of inheritance in order to provide genetic counseling.Methods:1. Clinical data were collected for analysis and blood samples were obtained from all patients and five relatives. The 4 cases were recorded as case 1,2,3,4.Case 1 and case 2 belonged to family A, case 3 and case 4 belonged to family B and C. Case 1 was the family propositus, and case 2 was her mother. Cases 3 and 4 were sporadic cases.2. Blood karyotype analysis was tested to exclude other chromosome diseases.3. The MECP2 gene was detected by PCR amplifying and sequencing to clarify the etiology and genetic pathwaysResults:1. All cases were diagnosed with Rett syndrome according to the 2010 latest diagnostic criteria and genetic diagnosis. Case 1 and 2 were atypical RTT, and case 3 and 4 were typical RTT.2. The karyotype analysis of 4 cases and 5 relatives were all normal.3. Case 1 and 2 were the first report of both mother and daughter with RTT in China, who were detected with a rare MECP2 gene heterozygous frameshift mutation:c.1157-1200 del 44 bp, which result of the amino-acid chain short. Case 3 and 4 were identified with two hotspot heterozygous nonsense mutations:c.808 C> T, c.502 C> T, the amino acid changes recorded as R270X、R168X.Conclusions:1. Gene analysis has enoumous value in diagnosing RTT especially in atypical cases.2. The MECP2 gene mutations of 4 cases in our study were all reported pathogenic mutations. Case 1 and case 2 were detected with heterozygous frameshift mutations, case 3 and case 4 were detected with hotspot nonsense mutations. They were the first reported RTT diagnosed by gene in southwest China.3. Taking a MECP2 gene analysis can reduce medical costs, carry out rehabilitation therapy earlier for RTT patients, and get genetic counseling for RTT family members. |
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