The p.Pro482Ala Variant in the CNNM2 Gene Causes Severe Hypomagnesemia Amenable to Treatment with Spironolactone
Renal hypomagnesemia syndromes involving <i>CNNM2</i> protein pathogenic variants are associated with variable degrees of neurocognitive dysfunction and hypomagnesemia. Here, we report a family with a novel <i>CNNM2</i> p.Pro482Ala variant, presenting with overt hypomagnesemi...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/13/7284 |
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| author | Ioannis Petrakis Eleni Drosataki Ioanna Stavrakaki Kleio Dermitzaki Dimitra Lygerou Myrto Konidaki Christos Pleros Nikolaos Kroustalakis Sevasti Maragkou Ariadni Androvitsanea Ioannis Stylianou Ioannis Zaganas Kostas Stylianou |
| author_facet | Ioannis Petrakis Eleni Drosataki Ioanna Stavrakaki Kleio Dermitzaki Dimitra Lygerou Myrto Konidaki Christos Pleros Nikolaos Kroustalakis Sevasti Maragkou Ariadni Androvitsanea Ioannis Stylianou Ioannis Zaganas Kostas Stylianou |
| author_sort | Ioannis Petrakis |
| collection | DOAJ |
| description | Renal hypomagnesemia syndromes involving <i>CNNM2</i> protein pathogenic variants are associated with variable degrees of neurocognitive dysfunction and hypomagnesemia. Here, we report a family with a novel <i>CNNM2</i> p.Pro482Ala variant, presenting with overt hypomagnesemia and mild neurological involvement (autosomal dominant renal hypomagnesemia 6, HOMG6, MIM# 613882). Using a bioinformatics approach, we showed that the p.Pro482Ala amino acid substitution causes a 3D conformational change in <i>CNNM2</i> structure in the cystathionin beta synthase (CBS) domain and the carboxy-terminal protein segment. A novel finding was that aldosterone inhibition with spironolactone helped to alleviate hypomagnesemia and symptoms in the proband. |
| first_indexed | 2024-03-09T21:48:58Z |
| format | Article |
| id | doaj.art-758b16de7ebe4fe3b217204477a103ba |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:48:58Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-758b16de7ebe4fe3b217204477a103ba2023-11-23T20:11:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012313728410.3390/ijms23137284The p.Pro482Ala Variant in the CNNM2 Gene Causes Severe Hypomagnesemia Amenable to Treatment with SpironolactoneIoannis Petrakis0Eleni Drosataki1Ioanna Stavrakaki2Kleio Dermitzaki3Dimitra Lygerou4Myrto Konidaki5Christos Pleros6Nikolaos Kroustalakis7Sevasti Maragkou8Ariadni Androvitsanea9Ioannis Stylianou10Ioannis Zaganas11Kostas Stylianou12Nephrology Department, Heraklion University Hospital, 71500 Heraklion, GreeceNephrology Department, Heraklion University Hospital, 71500 Heraklion, GreeceNephrology Department, Heraklion University Hospital, 71500 Heraklion, GreeceNephrology Department, Heraklion University Hospital, 71500 Heraklion, GreeceNephrology Department, Heraklion University Hospital, 71500 Heraklion, GreeceNephrology Department, Heraklion University Hospital, 71500 Heraklion, GreeceNephrology Department, Heraklion University Hospital, 71500 Heraklion, GreeceNephrology Department, Heraklion University Hospital, 71500 Heraklion, GreeceNephrology Department, Heraklion University Hospital, 71500 Heraklion, GreeceNephrology Department, Heraklion University Hospital, 71500 Heraklion, GreeceInstitute of Applied and Computational Mathematics of FORTH (Foundation of Research and Technology-Hellas), 70013 Heraklion, GreeceNeurogenetics Laboratory Medical School, University of Crete, 71003 Heraklion, GreeceNephrology Department, Heraklion University Hospital, 71500 Heraklion, GreeceRenal hypomagnesemia syndromes involving <i>CNNM2</i> protein pathogenic variants are associated with variable degrees of neurocognitive dysfunction and hypomagnesemia. Here, we report a family with a novel <i>CNNM2</i> p.Pro482Ala variant, presenting with overt hypomagnesemia and mild neurological involvement (autosomal dominant renal hypomagnesemia 6, HOMG6, MIM# 613882). Using a bioinformatics approach, we showed that the p.Pro482Ala amino acid substitution causes a 3D conformational change in <i>CNNM2</i> structure in the cystathionin beta synthase (CBS) domain and the carboxy-terminal protein segment. A novel finding was that aldosterone inhibition with spironolactone helped to alleviate hypomagnesemia and symptoms in the proband.https://www.mdpi.com/1422-0067/23/13/7284hypomagnesemiaHOMG6CNNM2whole exome sequencing |
| spellingShingle | Ioannis Petrakis Eleni Drosataki Ioanna Stavrakaki Kleio Dermitzaki Dimitra Lygerou Myrto Konidaki Christos Pleros Nikolaos Kroustalakis Sevasti Maragkou Ariadni Androvitsanea Ioannis Stylianou Ioannis Zaganas Kostas Stylianou The p.Pro482Ala Variant in the CNNM2 Gene Causes Severe Hypomagnesemia Amenable to Treatment with Spironolactone International Journal of Molecular Sciences hypomagnesemia HOMG6 CNNM2 whole exome sequencing |
| title | The p.Pro482Ala Variant in the CNNM2 Gene Causes Severe Hypomagnesemia Amenable to Treatment with Spironolactone |
| title_full | The p.Pro482Ala Variant in the CNNM2 Gene Causes Severe Hypomagnesemia Amenable to Treatment with Spironolactone |
| title_fullStr | The p.Pro482Ala Variant in the CNNM2 Gene Causes Severe Hypomagnesemia Amenable to Treatment with Spironolactone |
| title_full_unstemmed | The p.Pro482Ala Variant in the CNNM2 Gene Causes Severe Hypomagnesemia Amenable to Treatment with Spironolactone |
| title_short | The p.Pro482Ala Variant in the CNNM2 Gene Causes Severe Hypomagnesemia Amenable to Treatment with Spironolactone |
| title_sort | p pro482ala variant in the cnnm2 gene causes severe hypomagnesemia amenable to treatment with spironolactone |
| topic | hypomagnesemia HOMG6 CNNM2 whole exome sequencing |
| url | https://www.mdpi.com/1422-0067/23/13/7284 |
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