[Analysis of molecular genetics and clinical characteristics of 3 children with Waardenburg syndrome].

Objective:To analyze the molecular genetics and clinical characteristics of 3 children with syndromic deafness were analyzed to clarify their causative genes and genetic characteristics. Methods:The medical records of 3 children and their parents were collected and analyzed, including physical examination, hearing evaluation, temporal bone CT, and cranial MRI. Whole-exome sequencing（WES） was used to screen for pathogenic gene variants, and Sanger sequencing was used to verify the candidate positive variants in the probands and their parents. Results:All 3 patients were female with normal intelligence. Patient 1 and 3 had a family history of deafness, which conformed to the pattern of autosomal dominant inheritance. All three patients had bilateral profound sensorineural hearing impairment with bright-blue sclera. Other phenotypes included hypertelorism（patient 1）, multiple dyschromatosis（patient 2）, and yellowish hair（patient 2）, blepharoptosis（patient 3）. Patient 3 had bilateral vestibular enlargement, internal auditory canal enlargement, and bilateral inner ear malformations. Mother of patient 1 had only left mild hearing impairment; mother of patient 3 had bilateral hearing impairment with unilateral bright-blue sclera and yellowish hair. WES detected heterozygous variants, PAX3 c.811C>T, MITF c.632T>C, and SOX10 c.1359_1360 insGCCCCACA, in patient 1, 2, and 3, respectively. The variants in patient 1 and 3 were inherited from their mothers who had hearing impairment, and MITFvariant in patient 2 may be a spontaneous variation. The final diagnoses were that patient 1 with Waardenburg syndrome type 1（WS1）, and the mother of patient 1, patient 2, patient 3, and the mother of patient 3 with WS2. Conclusion:WS is a syndromic deafness, and the main clinical features include autosomal dominant inheritance and scleral pigment abnormalities. However, the findings of this study show that there is still phenotypic heterogeneity in WS even caused by the same gene variant, so it depends on genetic tests to confirm the diagnosis; The gene variant of patient 1 and 2 was never been reported in other patients, which expands the pathogenic variant spectrum of WS.

[Identification of novel pathogenic variants of TRIOBP gene in a pedigree affected with non-syndromic deafness].

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with non-syndromic hearing loss (NSHL). METHODS: Commercialized gene chip was applied to detect common mutations associated with congenital deafness. Whole exome sequencing was carried out for patients for whom gene chip yielded a negative result. Candidate variants were verified by Sanger sequencing. RESULTS: Two patients from the pedigree were discovered to carry compound heterozygous variants of the TRIOBP gene, namely c.3299C>A and c.5185-2A>G. Their parents had normal hearing and were both heterozygous carriers of the above variants. Both variants had co-segregated with the disease phenotype in the pedigree and were unreported previously. CONCLUSION: Pathogenic variants of the TRIOBP gene comprise an important factor for NSHL. The novel c.5185-2A>G and c.3299C>A variants discovered in this study have enriched the mutational spectrum of the TRIOBP gene and enabled molecular diagnosis and genetic counseling for the family.

[Exploration of the correlation between allergic rhinitis and weather factors in Nanning].

Objective:To investigate the characteristics of allergic rhinitis（AR） in the Nanning area and its correlation with meteorological factors. Methods:The characteristics of 16 969 cases of AR in Nanning from May 2011 to June 2018 were analyzed. Meteorological parameters were collected from the official website of the Nanning Meteorological Bureau, including weather conditions, temperature, and wind direction. The relationship between the onset characteristics of AR patients and meteorological factors were also analyzed. Results:Among the 16 969 patients with AR, the top three inhalation allergens were dust mite（56.0%）, house dust mite（50.5%）, and cockroach（37.4%）. The skin index（SI） of dust mite, house dust mite, cockroach is correlated with sex. The SI of dust mite, house dust mite, mugwort, cockroach are correlated with age, and inhaled allergens are correlated with disease course（P<0.05）. However, those relationships were not significant（r<0.2）. The proportion of AR patients visiting the clinic in summer was the highest（3.9%） in all of the four seasons. Gender was found to be related to the grade-4 positive results of dust mite（OR=0.826, 95%CI: 0.724-0.942）, the grade-4 house dust mite（OR=0.777, 95%CI: 0.677-0.891） and the grade-3 positive results of cockroach（OR=1.236, 95%CI: 1.060-1.443）, respectively. The the daytime weather conditions were related to the grade-4 positive results of dust mite（OR=0.830, 95%CI: 0.728-0.947） and the grade 1 positive results of house dust mite（OR=0.803, 95%CI: 0.694-0.929）, respectively. The highest temperature was related to the grade-4 positive result of dust mite（OR=1.032, 95%CI: 1.020-1.043）, grade-1（OR=1.028, 95%CI: 1.001-1.056） and grade-4 （OR=1.047, 95%CI: 1.021-1.075） positive result of house dust mite, grade 1（OR=1.023, 95%CI: 1.001-1.047） and grade-4（OR=1.050, 95%CI: 1.008-1.094） positive result of cockroach, respectively. The minimum temperature was related to the positive results of house dust mites at all grades and the grade-1 positive results of cockroach（OR=0.947, 95%CI: 0.924-0.971）, but not to dust mites. The daytime wind direction was related to the grade-3 positive results of cockroach（OR=1.437, 95%CI: 1.157-1.785）. Conclusion:The number of AR patients in Nanning is highest in summer. The female is more likely to suffer from dust mite and house dust mite, while the male is more likely to suffer from cockroach. Meteorological factors are correlated with the incidence of AR.The highertemperature, the rain and the southerly wind could cause the occurrence or aggravation of AR.

[Analysis common gene mutation spots of 127 non-syndromic deafness natients in Guangxi Drovince].

OBJECTIVE: To investigate the mutation characteristics of common deafness gene from 127 non-syndromic hearing loss patients in Guangxi province. METHOD: Deafness-related gene mutations detection kit was used to detect 15 mutation sites in four deafness-associated genes, and a total of 127 hearing impaired patients were tested. The samples that could not be diagnosed with DNA microarray were subjected to PCR and sequenced to detect other mutations. RESULT: Among the 127 patients with non-syndromic deafness, the total mutation rate is 8.66% (11/127), including GJB2 235delC homozygous in 3 cases (2.36%), 235delC single heterozygous mutation in 2 cases (1.57%), GJB2 235delC and 109 A > G mutations in 2 cases (1.57%); SLC26A4 1229C > T homozygous in 1 case (0.79%), IVS7-2A > G, IVS11 + 47T > C and 15448insC mutaion in 2 cases (1.57%); mitochondrial 12S rRNA gene mutations were not detected. The result indicates that GJB2 and SLC26A4 were the main genes in this study, and the mutation rate is significantly lower than the national average level. Three new mutations (SLC26A4 IVS11 + 47T > C,1548insC and GJB2 109A > G) were found. There may be rare mutations among sites or genes associated with deafness in Guangxi.