Genome sequencing identifies monogenic causes in adults with metabolic diseases

Clinical genome sequencing in 560 adults with common metabolic diseases, 17% actionable monogenic diagnostic yield

Clinical genome sequencing is performed in 560 adults with common metabolic diseases (hyperlipidemia, hypertriglyceridemia, prediabetes, type 2 diabetes, hypothyroidism) seen in New York clinical practices between 2020 and 2023. A diagnostic yield of 17% is observed for actionable monogenic variants. Most frequent diagnoses include familial hypercholesterolemia, MODY, and congenital hypothyroidism, with management changes in the majority of diagnosed cases.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

17% actionable monogenic causes behind apparent 'common disease' presentations: a figure strongly supporting extension of WGS to adults consulting in endocrinology/metabolism, particularly with family history or therapeutic resistance. These diagnoses radically change treatment (e.g., statins ineffective if PCSK9 gain of function) and have implications for relatives.

Clinical impact: 3/3 · Evidence strength: 3/3 · Novelty: 1/2 · Sample size: 1/1 · Publication status: 0/1 → Total: 8/10