RESUMO
Mitochondrial 12S rRNA A1555G and C1494T mutations are the major contributors to hearing loss. As patients with these mutations are sensitive to aminoglycosides, mutational screening for 12S rRNA is therefore recommended before the use of aminoglycosides. Most recently, we developed a novel multiplex allele-specific PCR (MAS-PCR) that can be used for detecting A1555G and C1494T mutations. In the present study, we employed this MAS-PCR to screen the 12S rRNA mutations in 500 deaf patients and 300 controls from 5 community hospitals. After PCR and electrophoresis, two patients with A1555G and one patient with C1494T were identified, this was consistent with Sanger sequence results. We further traced the origin of three Chinese pedigrees. Clinical evaluation revealed variable phenotypes of hearing loss including severity, age at onset and audiometric configuration in these patients. Sequence analysis of the mitochondrial genomes from matrilineal relatives suggested the presence of three evolutionarily conserved mutations: tRNACys T5802C, tRNALys A8343G and tRNAThr G15930A, which may result the failure in tRNAs metabolism and lead to mitochondrial dysfunction that was responsible for deafness. However, the lack of any functional variants in GJB2, GJB3, GJB6 and TRMU suggested that nuclear genes may not play active roles in deafness expression. Hence, aminoglycosides and mitochondrial genetic background may contribute to the clinical expression of A1555G/C1494T-induced deafness. Our data indicated that the MAS-PCR was a fast, convenience method for screening the 12S rRNA mutations, which was useful for early detection and prevention of mitochondrial deafness.
Assuntos
Análise Mutacional de DNA , Surdez/diagnóstico , Audição/genética , Reação em Cadeia da Polimerase Multiplex , Mutação , RNA Mitocondrial/genética , RNA Ribossômico/genética , Adulto , Idade de Início , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , China , Surdez/etnologia , Surdez/genética , Surdez/fisiopatologia , Feminino , Predisposição Genética para Doença , Hereditariedade , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVE: To study the clinicopathologic features and immunophenotype of renal cell carcinomas, and to discuss their diagnostic value. METHODS: The clinicopathologic features of 114 cases of renal cell carcinoma were reviewed and categorized on the basis of 2004 WHO classification. Immunohistochemical study for a panel of antibodies (including CK, CD10, vimentin, CD117, AMACR, CK7 and TFE3) was carried out. The follow-up data, if available, were also analyzed. RESULTS: The cases were reclassified into 5 subtypes, including 77 cases (67.5%) of clear cell carcinoma (CCRCC), 11 cases (9.6%) of papillary renal cell carcinoma (PRCC), 14 cases (12.3%) of chromophobe renal cell carcinoma (chrRCC), 10 cases (8.8%) of renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions (Xp11.2RCC) and 2 cases (1.8%) of unclassified renal cell carcinoma (unRCC). Immunohistochemical study showed that the expression rates of CK, CD10 and vimentin in CCRCC were 93.5% (72/77), 93.5% (72/77) and 75.3% (58/77), respectively. On the other hand, all the 11 cases of PRCC studied were positive for AMACR. The expression rate of CD117 in chrRCC was 78.5% (11/14). In the 10 cases of Xp11.2 RCC studied, the expression rates of TFE3, AMACR, CD10 and CK were 100% (10/10), 100% (10/10), 90% (9/10) and 70% (7/10), respectively. CONCLUSIONS: The various subtypes of renal cell carcinomas are heterogeneous in histologic appearance and demonstrate distinctive immunophenotype. The expressions of CD10, vimentin, CD117, AMACR, CK7 and TFE3 are helpful in the differential diagnosis.