Novel CFTR Missense Mutations in Brazilian Patients With Congenital Absence of Vas Deferens: Counseling Issues.

Pieri, Patrícia de Campos; Missaglia, Mariangela Tuzzollo; Roque, Juliana de Almeida; Moreira-Filho, Carlos Alberto; Hallak, Jorge

doi:10.1590/s1807-59322007000400003

Cited by 3 publications

(3 citation statements)

References 14 publications

(12 reference statements)

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“…In modern molecular medicine, genetic screening is an increasingly useful tool 35 that is currently applied to inherited tumor syndromes such as multiple endocrine neoplasia types 1 36 and 2. 31 …”

Section: Discussionmentioning

confidence: 99%

Sporadic Medullary Thyroid Carcinoma: Clinical Data From A University Hospital

Correia-Deur

Toledo

Imazawa

et al. 2009

Clinics

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INTRODUCTION:Medullary thyroid carcinoma may occur in a sporadic (s-medullary thyroid carcinoma, 75%) or in a multiple endocrine neoplasia type 2 form (MEN2, 25%). These clinical forms differ in many ways, as s-medullary thyroid carcinoma cases are RET-negative in the germline and are typically diagnosed later than medullary thyroid carcinoma in MEN2 patients. In this study, a set of cases with s-medullary thyroid carcinoma are documented and explored. PURPOSE: To document the phenotypes observed in s-medullary thyroid carcinoma cases from a university group and to attempt to improve earlier diagnosis of s-medullary thyroid carcinoma. Some procedures for diagnostics are also recommended. METHOD: Patients (n=26) with apparent s-medullary thyroid carcinoma were studied. Their clinical data were reviewed and peripheral blood was collected and screened for RET germline mutations. RESULTS:The average age at diagnosis was 43.9 years (± 10.82 SD) and did not differ between males and females. Calcitonin levels were increased in all cases. Three patients presented values that were 100-fold greater than the normal upper limit. Most (61.54%) had values that were 20-fold below this limit. Carcinoembryonic antigen levels were high in 70.6% of cases. There was no significant association between age at diagnosis, basal calcitonin levels or time of disease onset with thyroid tumor size (0.6-15 cm). Routine thyroid cytology yielded disappointing diagnostic accuracy (46.7%) in this set of cases. After total thyroidectomy associated with extensive cervical lymph node resection, calcitonin values remained lower than 5 pg/mL for at least 12 months in eight of the cases (30.8%). Immunocyto-and histochemistry for calcitonin were positive in all analyzed cases. None of the 26 cases presented germline mutations in the classical hotspots of the RET proto-oncogene. CONCLUSION: Our cases were identified late. The basal calcitonin measurements and immunostaining for calcitonin were highly useful for diagnosing s-medullary thyroid carcinoma. The rate of complete patient recovery was low, and none of the parameters analyzed were useful predictors of the thyroid tumor size. Our findings support previous recommendations for routine serum calcitonin evaluation and immunostaining analysis involving single thyroid nodules.

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Section: Discussionmentioning

confidence: 99%

Sporadic Medullary Thyroid Carcinoma: Clinical Data From A University Hospital

Correia-Deur

Toledo

Imazawa

et al. 2009

Clinics

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“…The frequency of the rest of the mutations varies from one country to another, but their overall frequencies are less than 1%, and could be considered to be rare in Latin America (Pérez et al, 2007). The carrier-rate and mutationfrequencies vary widely in different populations, and so screening tests with high detection-rates for CFTR mutations have to consider the population's ethnicity (Pieri et al, 2007).…”

Section: Considerations For Cf Mutation Screening Testsmentioning

confidence: 99%

“…The atypical CBAVD phenotype, however, is caused by milder mutations, most of them very rare or even not yet described, and thus not included in the panel of CF mutations usually screened. It was proposed that only an extensive CFTR screening can detect rare mutations that are not found by conventional screenings and commercial tests, and can thus improve the diagnosis and care of CF and CAVD as well as the prevention of new cases through the use of reproductive technologies (Pieri et al, 2007).…”

Section: Considerations For Cf Mutation Screening Testsmentioning

confidence: 99%

Cystic Fibrosis and Infertility

Batitucci¹,

Perrone²,

Brunoro³

2012

Cystic Fibrosis - Renewed Hopes Through Research

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Non-neutral nonsynonymous single nucleotide polymorphisms in human ABC transporters: the first comparison of six prediction methods

Hao

Feng

Xiao

et al. 2011

Pharmacological Reports

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Nonsynonymous single nucleotide polymorphisms (nsSNPs) in coding regions that can lead to amino acid changes may cause alteration of protein function and account for susceptibility to disease and altered drug/xenobiotic response. Abundant nsSNPs have been found in genes coding for human ATP-binding cassette (ABC) transporters, but there is little known about the relationship between the genotype and phenotype of nsSNPs in these membrane proteins. In addition, it is unknown which prediction method is better suited for the prediction of non-neutral nsSNPs of ABC transporters. We have identified 2,172 validated nsSNPs in 49 human ABC transporter genes from the Ensembl genome database and the NCBI SNP database. Using six different algorithms, 41 to 52% of nsSNPs in ABC transporter genes were predicted to have functional impacts on protein function. Predictions largely agreed with the available experimental annotations. Overall, 78.5% of non-neutral nsSNPs were predicted correctly as damaging by SNAP, which together with SIFT and PolyPhen, was superior to the prediction methods Pmut, PhD-SNP, and Panther. This study also identified any amino acids that were likely to be functionally critical but have not yet been studied experimentally. There was significant concordance between the predicted results of SIFT and PolyPhen. Evolutionarily non-neutral (destabilizing) amino acid substitutions are predicted to be the basis for the pathogenic alteration of ABC transporter activity that is associated with disease susceptibility and altered drug/xenobiotic response.

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Novel CFTR Missense Mutations in Brazilian Patients With Congenital Absence of Vas Deferens: Counseling Issues.

Cited by 3 publications

References 14 publications

Sporadic Medullary Thyroid Carcinoma: Clinical Data From A University Hospital

Sporadic Medullary Thyroid Carcinoma: Clinical Data From A University Hospital

Cystic Fibrosis and Infertility

Non-neutral nonsynonymous single nucleotide polymorphisms in human ABC transporters: the first comparison of six prediction methods

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