title: Next generation sequencing in endocrine practice.
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.
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, University of Minnesota Masonic Children's Hospital, Minneapolis, MN 55454, USA.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Forlenza
authors.affiliation: Department of Pediatrics, Division of Genetics and Metabolism, University of Minnesota Masonic Children's Hospital, Minneapolis, MN 55454, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Calhoun
authors.affiliation: University of Minnesota Genomics Center, Minneapolis, MN 55455, USA.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Beckman
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, University of Minnesota Masonic Children's Hospital, Minneapolis, MN 55454, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Halvorsen
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, University of Minnesota Masonic Children's Hospital, Minneapolis, MN 55454, USA.
authors.forename: Elwaseila
authors.initials: E
authors.lastname: Hamdoun
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Zierhut
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, University of Minnesota Masonic Children's Hospital, Minneapolis, MN 55454, USA.
authors.forename: Kyriakie
authors.initials: K
authors.lastname: Sarafoglou
authors.affiliation: Division of Pediatric Endocrinology and Metabolism, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
authors.forename: Lynda E
authors.initials: LE
authors.lastname: Polgreen
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, University of Minnesota Masonic Children's Hospital, Minneapolis, MN 55454, USA.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Miller
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, University of Minnesota Masonic Children's Hospital, Minneapolis, MN 55454, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Nathan
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, University of Minnesota Masonic Children's Hospital, Minneapolis, MN 55454, USA. Electronic address: petry005@umn.edu.
authors.forename: Anna
authors.initials: A
authors.lastname: Petryk
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D004702:Endocrine Glands / Q000473:pathology*; D004700:Endocrine System Diseases / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control / Q000628:therapy; D004704:Endocrinology / Q000379:methods; D005820:Genetic Testing; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007014:Hypophosphatasia / Q000235:genetics / Q000473:pathology / Q000628:therapy; D009154:Mutation; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: C548267:ALPL protein, human; D000469:Alkaline Phosphatase
keywords: Adrenal; Gene; Gonad; Hormone; Hypophosphatasia; Mutation; PTH; Pituitary; Thyroid; Vitamin D