nPendred syndrome （PS） is characterized by autosomal recessive inheritance of goiter associated with a defect of iodide organification, hearing loss, enlargement of the vestibular aqueduct （EVA）, and mutations of ...nPendred syndrome （PS） is characterized by autosomal recessive inheritance of goiter associated with a defect of iodide organification, hearing loss, enlargement of the vestibular aqueduct （EVA）, and mutations of the SLC26A4 gene. However, not all EVA patients have PS or SLC26A4 mutations. Two mutant alleles of SLC26A4 are detected in 1/4 of North American or European EVA populations, one mutant allele is detected in another 1/4 of patient populations, and no mutations are de-tected in the other 1/2. The presence of two mutant al-leles of SLC26A4 is associated with abnormal iodide or-ganification, increased thyroid gland volume, increased severity of hearing loss, and bilateral EVA. The pres-ence of a single mutant allele of SLC26A4 is associated with normal iodide organification, normal thyroid gland volume, less severe hearing loss and either bilateral or unilateral EVA. When other underlying correlations are accounted for, the presence of a cochlear malformation or the size of EVA does not have an effect on hearing thresholds. This is consistent with observations of an Slc26a4 mutant mouse model of EVA in which hearing loss is independent of endolymphatic hydrops or in-ner ear malformations. Segregation analyses of EVA in families suggest that the patients carrying one mutant allele of SLC26A4 have a second, undetected mutant allele of SLC26A4, and the probability of a sibling hav-ing EVA is consistent with its segregation as an autoso-mal recessive trait. Patients without any mutations are an etiologically heterogeneous group in which siblings have a lower probability of having EVA. SLC26A4 muta-tion testing can provide prognostic information to guide clinical surveillance and management, as well as the probability of EVA affecting a sibling.展开更多
AIM： To explore the effect and significance of inhibitor of growth 1 （ING1） gene in carcinogenesis and progression of human sporadic colorectal cancer. METHODS： mRNA expression, mutation, and loss of heterozygosi...AIM： To explore the effect and significance of inhibitor of growth 1 （ING1） gene in carcinogenesis and progression of human sporadic colorectal cancer. METHODS： mRNA expression, mutation, and loss of heterozygosity （LOH） of ING1 gene in 35 specimens of sporadic colorectal cancer tissues and the matched normal mucous membrane tissues were detected by semi-quantitative reverse transcriptase-polymerase chain reaction （RT-PCR）, PCR-single strain conformation polymorphism （PCR-SSCP） and PCR-simple sequence length polymorphism （PCR-SSLP） using microsatellite markers, respectively. RESULTS： The average ratios of light intensities of p33^ING1b and p47^ING1a mRNA expression in the cancerous tissues were significantly lower than those in normal tissues. The difference between the two mRNA splices was not significant in the matched tissues. In addition, the ratios of light intensities of p33^ING1b and p47^ING1a mRNA expression in the cancerous tissues of Dukes＇ stages C and D were significantly lower than those in cancerous tissues of Dukes＇ stages A and B. However, no mutation of ING1 gene was detected in all 35 cases; only 4 cases of LOH （11.4%） were found. CONCLUSION： p33^ING1b and p47^ING1a mRNA expressions are closely related with the carcinogenesis and progression of human sporadic colorectal cancer. No mutation of ING1 gene is found, and there are only few LOH in sporadic colorectal cancers. These might not be the main reasons for the down regulation of ING1 expression. Its low expression may happen in transcription or post-transcription.展开更多
基金Supported by NIH intramural research funds Z01-DC-000039,Z01-DC-000060 and Z01-DC-000064,NIH grants R01-DK43495 and P30-DK34854Kansas State University CVM-SMILE and the Kansas City Area Life Science Institute
文摘nPendred syndrome （PS） is characterized by autosomal recessive inheritance of goiter associated with a defect of iodide organification, hearing loss, enlargement of the vestibular aqueduct （EVA）, and mutations of the SLC26A4 gene. However, not all EVA patients have PS or SLC26A4 mutations. Two mutant alleles of SLC26A4 are detected in 1/4 of North American or European EVA populations, one mutant allele is detected in another 1/4 of patient populations, and no mutations are de-tected in the other 1/2. The presence of two mutant al-leles of SLC26A4 is associated with abnormal iodide or-ganification, increased thyroid gland volume, increased severity of hearing loss, and bilateral EVA. The pres-ence of a single mutant allele of SLC26A4 is associated with normal iodide organification, normal thyroid gland volume, less severe hearing loss and either bilateral or unilateral EVA. When other underlying correlations are accounted for, the presence of a cochlear malformation or the size of EVA does not have an effect on hearing thresholds. This is consistent with observations of an Slc26a4 mutant mouse model of EVA in which hearing loss is independent of endolymphatic hydrops or in-ner ear malformations. Segregation analyses of EVA in families suggest that the patients carrying one mutant allele of SLC26A4 have a second, undetected mutant allele of SLC26A4, and the probability of a sibling hav-ing EVA is consistent with its segregation as an autoso-mal recessive trait. Patients without any mutations are an etiologically heterogeneous group in which siblings have a lower probability of having EVA. SLC26A4 muta-tion testing can provide prognostic information to guide clinical surveillance and management, as well as the probability of EVA affecting a sibling.
基金Supported by the Guangxi Provincial Scientific Fund for the Returned Overseas Chinese Scholars, No. 0342018Key Research Fund from Public Health Bureau of Guangxi, No. 200206
文摘AIM： To explore the effect and significance of inhibitor of growth 1 （ING1） gene in carcinogenesis and progression of human sporadic colorectal cancer. METHODS： mRNA expression, mutation, and loss of heterozygosity （LOH） of ING1 gene in 35 specimens of sporadic colorectal cancer tissues and the matched normal mucous membrane tissues were detected by semi-quantitative reverse transcriptase-polymerase chain reaction （RT-PCR）, PCR-single strain conformation polymorphism （PCR-SSCP） and PCR-simple sequence length polymorphism （PCR-SSLP） using microsatellite markers, respectively. RESULTS： The average ratios of light intensities of p33^ING1b and p47^ING1a mRNA expression in the cancerous tissues were significantly lower than those in normal tissues. The difference between the two mRNA splices was not significant in the matched tissues. In addition, the ratios of light intensities of p33^ING1b and p47^ING1a mRNA expression in the cancerous tissues of Dukes＇ stages C and D were significantly lower than those in cancerous tissues of Dukes＇ stages A and B. However, no mutation of ING1 gene was detected in all 35 cases; only 4 cases of LOH （11.4%） were found. CONCLUSION： p33^ING1b and p47^ING1a mRNA expressions are closely related with the carcinogenesis and progression of human sporadic colorectal cancer. No mutation of ING1 gene is found, and there are only few LOH in sporadic colorectal cancers. These might not be the main reasons for the down regulation of ING1 expression. Its low expression may happen in transcription or post-transcription.
