OBJECTIVETo explore the genetic cause for a Uyghur Chinese child with collodion skin.

METHODSG-banded chromosomal karyotyping was carried out for the child and his parents. High-throughput sequencing for 25 genes related to ichthyosis and ichthyosiform dermatosis was also performed for the child.

RESULTSNo karyotypic abnormality was found in the child and his parents. High-throughput sequencing has detected in the patient a previously described pathogenic mutation c.919C>T (p.Arg307Trp) and a novel c.856C>T (p.Arg286Trp) mutation in the TGM1 gene. By Sanger sequencing, the child was verified to have carried both mutations. His father was found to be a heterozygous carrier of the c.856C>T (p.Arg286Trp) mutation, while neither mutation was found in the mother.

CONCLUSIONCongenital ichthyosis associated with the TGM1 gene may show an autosomal recessive inheritance. The collodion condition of the child is probably due to the compound heterozygous mutations of the TGM1 gene.

Child ; Chromosome Banding ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Ichthyosis, Lamellar ; genetics ; Infant ; Karyotyping ; Mutation ; Transglutaminases ; genetics

Objective: The burden of chronic disease has been continuously increasing in China since the early 1980s. Besides the worsening of risk factors, the change in diagnostic criteria is very likely an important explanation for the increase in the prevalence of hypertension, hyperlipidemia and diabetes mellitus, three commonest, major chronic conditions that can lead to major vascular events and deaths. This study aims to estimate the contribution of changes in diagnostic criteria to the increase in the prevalence of the three conditions in China. Methods: The data from two representative nation-wide surveys in China in 2002 and 2009, with 145 254 and 8 813 adults included respectively, were used to estimate the prevalence rate of the three conditions and the proportion attributable to the change in diagnostic criteria around year 2000. The new and old cutoff values for hypertension, hyperlipidemia, and hyperglycemia were 140/90 and 160/95 mmHg (1 mmHg=0.133 kPa), 5.7 and 6.2 mmol/L, and 7.0 and 7.8 mmol/L, respectively. The prevalence was standardized according to the distribution of age, sex and rural-urban residence of the 2000 national census of the country so as to compare between the old and new diagnostic criteria and project the situation for the entire country. Results: The standardized prevalence of hypertension, hyperlipidemia, and diabetes mellitus for the entire Chinese adult population in 2002 was 8.21%, 1.71% and 1.43% according to the immediate previous diagnostic criteria, and 19.18%, 3.53% and 2.66% according to the new criteria. In 2009, the prevalence was 11.89%, 9.34% and 4.29% according to the old criteria, and 24.78%, 18.36% and 6.55% according to the new criteria. The total cumulative prevalence of the three conditions was increased by 124% in 2002 and 95% in 2009 as a result of change in diagnostic criteria. Put it differently, the change in diagnostic criteria increased the number of the three conditions from 2002 to 2009 by approximately 359 million and could increase the annual drug costs by some 271 billion RMB if all the conditions are treated. The drug costs alone of treating all the three conditions could consume 56% of the total health budget of the Government in 2010. Conclusion About half of the number of the three conditions is a result of the change in diagnostic criteria. These criteria were adopted from western populations, which are designed to meet the population need and suit healthcare resources available in these countries. It is important for China to consider the resources available and needs and values of the population in addition to the benefits, harms and costs of treatment in determining the cutoff values for defining these conditions for drug interventions.

Objective: To analyze the gene mutations and clinical features of patients with Noonan syndrome and hypertrophic cardiomyopathy. Method: Determined the mutation domain in five cases diagnosed with Noonan syndrome and hypertrophic cardiomyopathy and identified the relationship between the mutant domain and hypertrophic cardiomyopathy by searching relevant articles in pubmed database. Result: Three mutant genes (PTPN11 gene in chromosome 12, RIT1 gene in chromosome 1 and RAF1 gene in chromosome 3) in five cases all had been reported to be related to hypertrophic cardiomyopathy. The reported hypertrophic cardiomyopathy relevant genes MYPN, MYH6 and MYBP3 had also been found in case 1 and 2. Patients with same gene mutation had different clinical manifestations. Both case 4 and 5 had RAF1 mutation (c.770C>T). However, case 4 had special face, low IQ, mild pulmonary artery stenosis, and only mild ventricular hypertrophy. Conclusion Noonan syndrome is a genetic heterogeneity disease. Our study identified specific gene mutations that could result in Noonan syndrome with hypertrophic cardiomyopathy through molecular biology methods. The results emphasize the importance of gene detection in the management of Noonan syndrome.

OBJECTIVE: To analyze the clinical phenotype and genetic basis for a Chinese pedigree suspected for branchiootic syndrome (BOS). METHODS: The proband was subjected to target-capture high-throughput sequencing to detect potential variant of deafness-associated genes. Candidate variants were verified by Sanger sequencing of the family members. RESULTS: The proband was found to harbor a c.1627C>T (p.Gln543Ter) nonsense variant of the EYA1 gene. Sanger sequencing confirmed that all of the 4 patients with the BOS phenotype from the pedigree have harbored the same heterozygous variant. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PS+PP3+PP4). CONCLUSION The c.1627C>T (p.Gln543Ter) variant of the EYA1 gene probably underlay the BOS phenotype in this pedigree. Above finding has provided a basis for its clinical diagnosis.
Branchio-Oto-Renal Syndrome ; China ; Humans ; Intracellular Signaling Peptides and Proteins/genetics* ; Mutation ; Nuclear Proteins/genetics* ; Pedigree ; Protein Tyrosine Phosphatases/genetics*

Objective To investigate the clinical phenotype,sperm characteristics,genetic etiology and the outcomes of assisted repro-ductive technology of 2 minority patients(P1 Hui and P2 Uyghur)with globozoospermia.Methods The clinical data and various pa-rameters of semen examination in the 2 minority patients with globozoospermia were analyzed.The ultrastructure of their sperms was ob-served,and the genetic etiology of the patients was analyzed by whole exome sequencing(WES)and qPCR.Intracytoplasmic sperm in-jection(ICSI)combined with artificial oocyte activation(AOA)were applied for assisted reproduction thyrapy.The outcomes of assis-ted reproduction in the two couples were observed.Results Homozygous 109681 bp deletion in DPY19L2 gene was found in both the patients.The homozygous deletion of DPY19L2 gene in P2 patient came from his inbred parents.Low sperm motility and high sperm DNA fragmentation rate were observed in the P1 patient,the and the rate of round-headed sperm was 100％in morphology.The ab-sence of sperm acrosome and ultrastructural defects of plasma membrane,mitochondria and microtubules were found under the electron microscope.In the P2 patient,sperm motility and sperm DNA fragmentation rate patient were normal,and the sperm morphology was 100％round-headed sperm.Under the electron microscope,the main defects of sperm were small and round head with acrosomal ab-sence,structural damage,but the ultrastructural defects of organelles were rare,such as plasma membrane,mitochondria and microtu-bules.Both couples of the two patients received ICSI+AOA for assisted pregnancy,and the ICSI fertilization rate was 62.5％for P1 pa-tient and 75％for P2 patient.Both the patients successfully obtained clinical pregnancy.Conclusion The abnormal DPY19L2 gene is the main genetic cause in the globozoospermia patients with different ethnic backgrounds.Both structural damage and ultrastructural de-fects of organelles such as plasma membrane,mitochondrial and microtubule damage could be found in globozoospermia.ICSI combined with AOA should be an effective assisted reproductive thyrapy strategy for the patients with globozoospermia.