Low HbA1c With Normal Hemoglobin in a Diabetes Patient Caused by PIEZO1 Gene Variant: A Case Report

Song, An; Lin, Liwu; Li, Yuxiu; Lin, Michael C.; Cheng, Xinqi; Xia, Weibo; Wang, Ou; Xing, Xiaoping

doi:10.3389/fendo.2020.00356

Cited by 4 publications

(3 citation statements)

References 26 publications

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“…One of these variants, 16:88719665:G:A or T2127M (rs587776991) is a gain of function variant that slows down inactivation kinetics of PIEZO1 in patients with dehydrated hereditary stomatocytosis (a disorder of red blood cells), together with other gain of function variants 39 – 41 . Decreased levels of HbA1c had previously been observed in individuals with red blood cell disorders 42 – 44 .…”

Section: Resultsmentioning

confidence: 72%

Identifying interpretable gene-biomarker associations with functionally informed kernel-based tests in 190,000 exomes

et al. 2022

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Here we present an exome-wide rare genetic variant association study for 30 blood biomarkers in 191,971 individuals in the UK Biobank. We compare gene-based association tests for separate functional variant categories to increase interpretability and identify 193 significant gene-biomarker associations. Genes associated with biomarkers were ~ 4.5-fold enriched for conferring Mendelian disorders. In addition to performing weighted gene-based variant collapsing tests, we design and apply variant-category-specific kernel-based tests that integrate quantitative functional variant effect predictions for missense variants, splicing and the binding of RNA-binding proteins. For these tests, we present a computationally efficient combination of the likelihood-ratio and score tests that found 36% more associations than the score test alone while also controlling the type-1 error. Kernel-based tests identified 13% more associations than their gene-based collapsing counterparts and had advantages in the presence of gain of function missense variants. We introduce local collapsing by amino acid position for missense variants and use it to interpret associations and identify potential novel gain of function variants in PIEZO1. Our results show the benefits of investigating different functional mechanisms when performing rare-variant association tests, and demonstrate pervasive rare-variant contribution to biomarker variability.

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Section: Resultsmentioning

confidence: 72%

Identifying interpretable gene-biomarker associations with functionally informed kernel-based tests in 190,000 exomes

et al. 2022

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show abstract

“…One of these variants, 16:88719665:G:A or T2127M (rs587776991) is a gain of function variant that slows down inactivation kinetics of PIEZO1 in patients with dehydrated hereditary stomatocytosis (a disorder of red blood cells), together with other gain of function variants [39, 40]. Decreased levels of HbA1c had previously been observed in individuals with red blood cell disorders [41, 42, 43].…”

Section: Resultsmentioning

confidence: 99%

Identifying interpretable gene-biomarker associations with functionally informed kernel-based tests in 190,000 exomes

Monti

Rautenstrauch

et al. 2021

Preprint

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Here we present an exome-wide rare genetic variant association study for 30 biomarkers in 191,640 individuals in the UK Biobank. We perform gene-based association tests for separate functional variant categories to increase interpretability and identify 201 significant gene-biomarker associations, which include novel associations such as GIGYF1 with diabetes markers. In addition to performing gene-based variant collapsing tests, we design and apply variant-category-specific kernel-based tests that integrate quantitative functional variant effect predictions for missense variants, splicing and the binding of RNA-binding proteins. For these tests we present a powerful and computationally efficient combination of the likelihood-ratio and score tests that found 32% more associations than the score test alone. Kernel-based tests identified 12-31% more associations than their gene-based collapsing counterparts with large overlaps, and had advantages in the presence of gain of function missense variants. We introduce local collapsing by amino acid position for missense variants and use this approach to identify potential novel gain of function variants in PIEZO1, and interpret a position-specific association of ABCA1-variants with inflammation marker CRP. Our results show the benefits of separately investigating different functional mechanisms when performing rare-variant association tests, and highlight the strengths of biomarker panels for large biobanks.

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“… 23 In addition, in a recently reported case of diabetes mellitus with Piezo1 gene mutation, the level of glycosylated hemoglobin decreased, the level of glycosylated albumin was higher, and the levels of hemoglobin and albumin were normal. 91 …”

Section: The Effect Of Piezo1 On Cardiovascular Health Under Mechanic...mentioning

confidence: 99%

The Janus-faced role of Piezo1 in cardiovascular health under mechanical stimulation

Huang

Zhang

et al. 2023

Genes & Diseases

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Low HbA1c With Normal Hemoglobin in a Diabetes Patient Caused by PIEZO1 Gene Variant: A Case Report

Cited by 4 publications

References 26 publications

Identifying interpretable gene-biomarker associations with functionally informed kernel-based tests in 190,000 exomes

Identifying interpretable gene-biomarker associations with functionally informed kernel-based tests in 190,000 exomes

Identifying interpretable gene-biomarker associations with functionally informed kernel-based tests in 190,000 exomes

The Janus-faced role of Piezo1 in cardiovascular health under mechanical stimulation

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