PLIN1 Haploinsufficiency Is Not Associated With Lipodystrophy.

The Journal of Clinical Endocrinology and Metabolism
Thomas W LaverM N Weedon

Abstract

Monogenic partial lipodystrophy is a genetically heterogeneous disease where only variants with specific genetic mechanisms are causative. Three heterozygous protein extending frameshift variants in PLIN1 have been reported to cause a phenotype of partial lipodystrophy and insulin resistance. We investigated if null variants in PLIN1 cause lipodystrophy. As part of a targeted sequencing panel test, we sequenced PLIN1 in 2208 individuals. We also investigated the frequency of PLIN1 variants in the gnomAD database, and the type 2 diabetes knowledge portal. We identified 6/2208 (1 in 368) individuals with a PLIN1 null variant. None of these individuals had clinical or biochemical evidence of overt lipodystrophy. Additionally, 14/17,000 (1 in 1214) individuals with PLIN1 null variants in the type 2 diabetes knowledge portal showed no association with biomarkers of lipodystrophy. PLIN1 null variants occur too frequently in gnomAD (126/138,632; 1 in 1100) to be a cause of rare overt monogenic partial lipodystrophy. Our study suggests that heterozygous variants that are predicted to result in PLIN1 haploinsufficiency are not a cause of familial partial lipodystrophy and should not be reported as disease-causing variants by diagnostic ...Continue Reading

References

May 1, 2007·Experimental Cell Research·Howard J Worman, Gisèle Bonne
Dec 4, 2009·Genes and Immunity·J M M HowsonUNKNOWN Type I Diabetes Genetics Consortium
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
Oct 7, 2016·The Journal of Clinical Endocrinology and Metabolism·Rebecca J BrownTohru Yorifuji
May 19, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Nicola WhiffinJames S Ware
Oct 27, 2017·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Elaine ChiquettePraveen Dhankhar

❮ Previous
Next ❯

Citations

May 29, 2019·Current Opinion in Lipidology·Audrey MelvinDavid B Savage
May 23, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Christos BagiasStelios Tigas
Sep 11, 2019·The Journal of Clinical Endocrinology and Metabolism·Isabelle JéruCorinne Vigouroux
Dec 8, 2021·The Journal of Clinical Endocrinology and Metabolism·Mine KopruluDavid B Savage

❮ Previous
Next ❯

Methods Mentioned

BETA
targeted gene panel

Software Mentioned

gnomAD

Related Concepts

Related Feeds

Biomarkers for Type 2 Diabetes

Biomarkers can help understand chronic diseases and assist in risk prediction for prevention and early detection of diseases. Here is the latest research on biomarkers in type 2 diabetes, a disease in which the body is unable to produce or properly use insulin.