0.05). Conclusions MSI and LOH may play a certain role in the carcinogenesis and progression of arsenic-induced skin lesions.

Objectives To observe the frequencies of mutations at glycophorin A(GPA)of erythro-cytes in patients with high arsenic coal poisoning(HACP)in comparison with normal controls.Methods The peripheral erythrocytes were isolated and immunolabelled,and were detected by flow cytometry in40patients and18normal adults.Results The mutation frequencies(MF)were(21.23?13.97)?10 -6 for type NN,(33.13?25.72)?10 -6 for type NO,(110.90?63.58)?10 -6 for type MM,and(20.35?21.26)?10 -6 for type MO of erythrocytes in patients with HACP,which were significantly higher than those in normal controls.The mutation frequencies were(31.50?16.13)?10 -6 for type NN,(54.50?38.13)?10 -6 for type NO,(159.33?66.22)?10 -6 for type MM,and(45.16?12.69)?10 -6 for type MO of erythrocytes in tumor group of HACP patients,which were significantly higher than those of non-tumor group of the patients.Conclusions Arsenic poisoning may induce the mutation at the glycophorin-A locus of erythrocytes,sug-gesting that arsenic may be one of potential mutagens.GPA-MF may serve as a parameter for the detection of patients with HACP.

Objective To report a pedigree with X?linked dominant protoporphyria(XLDPP), and to detect 5?aminolevulinic acid synthetase 2(ALAS2)gene mutations in this pedigree. Methods A clinical investigation was performed in a pedigree with XLDPP, and relevant data were collected from family members. A next?generation sequencing method was applied to screen possible mutation sites, and Sanger sequencing was performed to determine pathogenic gene mutations. Dermoscopy was conducted to observe skin lesions in the patients with XLDPP, and the Fotofinder system and very high frequency (VHF) ultrasound system were utilized to assess the severity of photodamage. Liver and gallbladder ultrasonography as well as blood examination were performed for all the family members. Results A deletion mutation, c.1706?1709ΔAGTG, was detected in the ALAS2 gene on the X chromosomes of all the patients in this family, which led to replacement or loss of 19-20 C?terminal residues through transcriptional frameshifting, and eventually caused an increase in ALAS2 activity. In the patients with XLDPP, skin photodamage was relatively severe;protoporphyrin?induced hepatobiliary damage was observed and aggravated with age;anemia and iron deficiency occurred sometimes. Conclusion The deletion mutation c.1706?1709ΔAGTG of the ALAS2 gene may be the underlying cause of XLDPP in this pedigree.

Objective To investigate the prenatal diagnosis and genetic counseling of fetal nuchal fold (NF) thickening.Methods This study retrospectively analyzed 17 fetuses with increased NF detected by prenatal ultrasound examination in Peking Union Medical College Hospital,Peking Union Medical College & Chinese Academy of Medical Sciences from December 1,2016 to December 1,2017.All cases were divided into isolated (isolated group) or non-isolated increased NF group (non-isolated group) according to whether the fetus had concomitant ultrasonographic abnormalities or not.Karyotype and chromosomal microarray analysis (CMA) were performed on all cases.Clinical data,prenatal genetic testing results and pregnancy outcomes were analyzed.Results Of those twelve cases in the isolated group,two were terminated due to the identification of chromosomal abnormalities and pathogenic copy number variations (CNVs) and the fetal autopsy results were consistent with the prenatal diagnosis.The rest 10 pregnancies were all continued including one fetus carrying a variant of unknown significance,which was proved to be a paternal heredity by CMA,and nine without genetic abnormalities and all-these infants were healthy during follow-up.Among the five non-isolated cases,one was diagnosed as trisomy 21 by karyotyping and CMA,and the other four were found to have structural abnormalities under ultrasound scan,but without genetic abnormalities in karyotyping and CMA.And all the five pregnancies were terminated after genetic counseling and three of them chose whole exome sequencing (WES) for further test.One homozygous mutation in CHRNA 1 gene and one de novo mutation in SETD2 gene were found in two cases,respectively,while no abnormality was identified in the other one case.Conclusions Once increased NF were indicated by ultrasound examination,prenatal genetic testing should be offered to the patients,including CMA,regardless of other ultrasonographic abnormalities,and WES should also be offered when necessary.Considering a thickened NF is associated with increased risks of structural defects,a close follow-up with fetal echocardiography and ultrasound is required even the prenatal tests are normal.