Cargando…
Very Low Vitamin D in a Patient With a Novel Pathogenic Variant in the GC Gene That Encodes Vitamin D-Binding Protein
Circulating plasma vitamin D metabolites are highly bound to vitamin D-binding protein (DBP), also known as group-specific component or Gc-globulin. DBP, encoded by the GC gene, is a member of the albumin family of globular serum transport proteins. We previously described a homozygous GC gene delet...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362819/ https://www.ncbi.nlm.nih.gov/pubmed/34589658 http://dx.doi.org/10.1210/jendso/bvab104 |
_version_ | 1783738243984916480 |
---|---|
author | Banerjee, Ronadip R Spence, Tara Frank, Stuart J Pandian, Raj Hoofnagle, Andrew N Argiropoulos, Bob Marcadier, Julien L |
author_facet | Banerjee, Ronadip R Spence, Tara Frank, Stuart J Pandian, Raj Hoofnagle, Andrew N Argiropoulos, Bob Marcadier, Julien L |
author_sort | Banerjee, Ronadip R |
collection | PubMed |
description | Circulating plasma vitamin D metabolites are highly bound to vitamin D-binding protein (DBP), also known as group-specific component or Gc-globulin. DBP, encoded by the GC gene, is a member of the albumin family of globular serum transport proteins. We previously described a homozygous GC gene deletion in a patient with apparent severe vitamin D deficiency, fragility fractures, and ankylosing spondylitis. Here, we report an unrelated patient free of fractures or rheumatologic disease, but with very low 25-hydroxyvitamin D and 1,25-hydroxyvitamin D, as well as undetectable DBP measured by liquid chromatography–tandem mass spectrometry. A whole gene deletion was excluded by microarray, and Sanger sequencing of GC revealed a homozygous pathogenic variant affecting a canonical splice site (c0.702-1G > A). These findings indicate that loss of function variants in GC that eliminate DBP, and severely reduced total circulating vitamin D levels, do not necessarily result in significant metabolic bone disease. Together with our previous report, these cases support the free-hormone hypothesis, and suggest free vitamin D metabolites may serve as preferable indicators of bone and mineral metabolism, particularly when clinical suspicion of DBP deficiency is high. |
format | Online Article Text |
id | pubmed-8362819 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-83628192021-09-28 Very Low Vitamin D in a Patient With a Novel Pathogenic Variant in the GC Gene That Encodes Vitamin D-Binding Protein Banerjee, Ronadip R Spence, Tara Frank, Stuart J Pandian, Raj Hoofnagle, Andrew N Argiropoulos, Bob Marcadier, Julien L J Endocr Soc Case Reports Circulating plasma vitamin D metabolites are highly bound to vitamin D-binding protein (DBP), also known as group-specific component or Gc-globulin. DBP, encoded by the GC gene, is a member of the albumin family of globular serum transport proteins. We previously described a homozygous GC gene deletion in a patient with apparent severe vitamin D deficiency, fragility fractures, and ankylosing spondylitis. Here, we report an unrelated patient free of fractures or rheumatologic disease, but with very low 25-hydroxyvitamin D and 1,25-hydroxyvitamin D, as well as undetectable DBP measured by liquid chromatography–tandem mass spectrometry. A whole gene deletion was excluded by microarray, and Sanger sequencing of GC revealed a homozygous pathogenic variant affecting a canonical splice site (c0.702-1G > A). These findings indicate that loss of function variants in GC that eliminate DBP, and severely reduced total circulating vitamin D levels, do not necessarily result in significant metabolic bone disease. Together with our previous report, these cases support the free-hormone hypothesis, and suggest free vitamin D metabolites may serve as preferable indicators of bone and mineral metabolism, particularly when clinical suspicion of DBP deficiency is high. Oxford University Press 2021-06-05 /pmc/articles/PMC8362819/ /pubmed/34589658 http://dx.doi.org/10.1210/jendso/bvab104 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Case Reports Banerjee, Ronadip R Spence, Tara Frank, Stuart J Pandian, Raj Hoofnagle, Andrew N Argiropoulos, Bob Marcadier, Julien L Very Low Vitamin D in a Patient With a Novel Pathogenic Variant in the GC Gene That Encodes Vitamin D-Binding Protein |
title | Very Low Vitamin D in a Patient With a Novel Pathogenic Variant in the
GC Gene That Encodes Vitamin D-Binding Protein |
title_full | Very Low Vitamin D in a Patient With a Novel Pathogenic Variant in the
GC Gene That Encodes Vitamin D-Binding Protein |
title_fullStr | Very Low Vitamin D in a Patient With a Novel Pathogenic Variant in the
GC Gene That Encodes Vitamin D-Binding Protein |
title_full_unstemmed | Very Low Vitamin D in a Patient With a Novel Pathogenic Variant in the
GC Gene That Encodes Vitamin D-Binding Protein |
title_short | Very Low Vitamin D in a Patient With a Novel Pathogenic Variant in the
GC Gene That Encodes Vitamin D-Binding Protein |
title_sort | very low vitamin d in a patient with a novel pathogenic variant in the
gc gene that encodes vitamin d-binding protein |
topic | Case Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362819/ https://www.ncbi.nlm.nih.gov/pubmed/34589658 http://dx.doi.org/10.1210/jendso/bvab104 |
work_keys_str_mv | AT banerjeeronadipr verylowvitamindinapatientwithanovelpathogenicvariantinthegcgenethatencodesvitamindbindingprotein AT spencetara verylowvitamindinapatientwithanovelpathogenicvariantinthegcgenethatencodesvitamindbindingprotein AT frankstuartj verylowvitamindinapatientwithanovelpathogenicvariantinthegcgenethatencodesvitamindbindingprotein AT pandianraj verylowvitamindinapatientwithanovelpathogenicvariantinthegcgenethatencodesvitamindbindingprotein AT hoofnagleandrewn verylowvitamindinapatientwithanovelpathogenicvariantinthegcgenethatencodesvitamindbindingprotein AT argiropoulosbob verylowvitamindinapatientwithanovelpathogenicvariantinthegcgenethatencodesvitamindbindingprotein AT marcadierjulienl verylowvitamindinapatientwithanovelpathogenicvariantinthegcgenethatencodesvitamindbindingprotein |