Molecular diagnosis in the clinical practice: an endocrinologist’s perspective

Resumo

Endocrinology is one of several medical specialities that have been gradually transformed by a deeper understanding of the molecular bases of disorders. Genetic testing with the purposes of defining a precise molecular diagnosis has increasingly gained space in the routine assessment of patients with endocrinopathies, and the advent of massive parallel sequencing (MPS) is boosting the incorporation of molecular information in the clinic. The main benefit of genetic testing is diagnostic precision, resulting in improved and individualized care for patients and family members, and better disease prevention. However, genetic tests are not infallible and may bear several potential risks, being thus indicated when clinical suspicion is strong and the benefit of determining a molecular diagnosis is unambiguous. In this review, these evolving concepts and current indications for molecular diagnosis in endocrinology will be explored. Molecular tools will be revised and contextualised, including those aimed at identifying changes in gene dosage (karyotpe, FISH, MLPA, aCGH, SNParray) or in the DNA nucleotide sequence (allele-specific PCR, RFLP, Sanger sequencing, MPS or NGS). Finally, matters surrounding the complex attribution of biologically relevant functional impact to identified DNA variants will be explored, together with the challenges brought by high throughput molecular analysis. These are exciting times for molecular endocrinology, and hopefully soon a translation to multiple benefits for patients will be self-evident.