Next generation sequencing in endocrine practice

Mol Genet Metab. 2015 Jun-Jul;115(2-3):61-71. doi: 10.1016/j.ymgme.2015.05.002. Epub 2015 May 3.

Abstract

With the completion of the Human Genome Project and advances in genomic sequencing technologies, the use of clinical molecular diagnostics has grown tremendously over the last decade. Next-generation sequencing (NGS) has overcome many of the practical roadblocks that had slowed the adoption of molecular testing for routine clinical diagnosis. In endocrinology, targeted NGS now complements biochemical testing and imaging studies. The goal of this review is to provide clinicians with a guide to the application of NGS to genetic testing for endocrine conditions, by compiling a list of established gene mutations detectable by NGS, and highlighting key phenotypic features of these disorders. As we outline in this review, the clinical utility of NGS-based molecular testing for endocrine disorders is very high. Identifying an exact genetic etiology improves understanding of the disease, provides clear explanation to families about the cause, and guides decisions about screening, prevention and/or treatment. To illustrate this approach, a case of hypophosphatasia with a pathogenic mutation in the ALPL gene detected by NGS is presented.

Keywords: Adrenal; Gene; Gonad; Hormone; Hypophosphatasia; Mutation; PTH; Pituitary; Thyroid; Vitamin D.

Publication types

  • Review

MeSH terms

  • Alkaline Phosphatase / genetics
  • Endocrine Glands / pathology*
  • Endocrine System Diseases / etiology
  • Endocrine System Diseases / genetics*
  • Endocrine System Diseases / prevention & control
  • Endocrine System Diseases / therapy
  • Endocrinology / methods
  • Genetic Testing
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Hypophosphatasia / genetics
  • Hypophosphatasia / pathology
  • Hypophosphatasia / therapy
  • Mutation*
  • Sequence Analysis, DNA / methods*

Substances

  • ALPL protein, human
  • Alkaline Phosphatase