Comparison of flow-FISH and MM-qPCR telomere length assessment techniques for the screening of telomeropathies.
Ann N Y Acad Sci
; 1466(1): 93-103, 2020 04.
Article
en En
| MEDLINE
| ID: mdl-31647584
ABSTRACT
Assessment of telomere length (TL) in peripheral blood leukocytes is part of the diagnostic algorithm applied to patients with acquired bone marrow failure syndromes (BMFSs) and dyskeratosis congenita (DKC). Monochrome multiplex-quantitative polymerase chain reaction (MM-qPCR) and fluorescence in situ hybridization (flow-FISH) are methodologies available for TL screening. Dependent on TL expressed in relation to percentiles of healthy controls, further genetic testing for inherited mutations in telomere maintenance genes is recommended. However, the correct threshold to trigger this genetic workup is still under debate. Here, we prospectively compared MM-qPCR and flow-FISH regarding their capacity for accurate identification of DKC patients. All patients (n = 105) underwent genetic testing by next-generation sequencing and in 16 patients, mutations in DKC-relevant genes were identified. Whole leukocyte TL of patients measured by MM-qPCR was found to be moderately correlated with lymphocyte TL measured by flow-FISH (r² = 0.34; P < 0.0001). The sensitivity of both methods was high, but the specificity of MM-qPCR (29%) was significantly lower compared with flow-FISH (58%). These results suggest that MM-qPCR of peripheral blood cells is inferior to flow-FISH for clinical routine screening for suspected DKC in adult patients with BMFS due to lower specificity and a higher rate of false-positive results.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Telómero
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Hibridación Fluorescente in Situ
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Reacción en Cadena de la Polimerasa Multiplex
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Homeostasis del Telómero
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Enfermedades Genéticas Congénitas
Tipo de estudio:
Diagnostic_studies
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Etiology_studies
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Evaluation_studies
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Incidence_studies
/
Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Ann N Y Acad Sci
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania