Hypomagnesaemia with varying degrees of extrarenal symptoms as a consequence of heterozygous CNNM2 variants
© 2024. The Author(s)..
Variants in the CNNM2 gene are causative for hypomagnesaemia, seizures and intellectual disability, although the phenotypes can be variable. This study aims to understand the genotype-phenotype relationship in affected individuals with CNNM2 variants by phenotypic, functional and structural analysis of new as well as previously reported variants. This results in the identification of seven variants that significantly affect CNNM2-mediated Mg2+ transport. Pathogenicity of these variants is further supported by structural modelling, which predicts CNNM2 structure to be affected by all of them. Strikingly, seizures and intellectual disability are absent in 4 out of 7 cases, indicating these phenotypes are caused either by specific CNNM2 variant only or by additional risk factors. Moreover, in line with sporadic observations from previous reports, CNNM2 variants might be associated with disturbances in parathyroid hormone and Ca2+ homeostasis.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
|---|---|
| Enthalten in: |
Scientific reports - 14(2024), 1 vom: 22. März, Seite 6917 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Bosman, Willem [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
CNNM2 |
|---|
| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 25.03.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41598-024-57061-7 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370090985 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370090985 | ||
| 003 | DE-627 | ||
| 005 | 20240325235556.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240324s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41598-024-57061-7 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1347.xml |
| 035 | |a (DE-627)NLM370090985 | ||
| 035 | |a (NLM)38519529 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Bosman, Willem |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Hypomagnesaemia with varying degrees of extrarenal symptoms as a consequence of heterozygous CNNM2 variants |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 25.03.2024 | ||
| 500 | |a Date Revised 25.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Variants in the CNNM2 gene are causative for hypomagnesaemia, seizures and intellectual disability, although the phenotypes can be variable. This study aims to understand the genotype-phenotype relationship in affected individuals with CNNM2 variants by phenotypic, functional and structural analysis of new as well as previously reported variants. This results in the identification of seven variants that significantly affect CNNM2-mediated Mg2+ transport. Pathogenicity of these variants is further supported by structural modelling, which predicts CNNM2 structure to be affected by all of them. Strikingly, seizures and intellectual disability are absent in 4 out of 7 cases, indicating these phenotypes are caused either by specific CNNM2 variant only or by additional risk factors. Moreover, in line with sporadic observations from previous reports, CNNM2 variants might be associated with disturbances in parathyroid hormone and Ca2+ homeostasis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CNNM2 | |
| 650 | 4 | |a Genetic hypomagnesaemia | |
| 650 | 4 | |a Intellectual disability | |
| 650 | 4 | |a Variant characterisation | |
| 650 | 7 | |a Magnesium |2 NLM | |
| 650 | 7 | |a I38ZP9992A |2 NLM | |
| 650 | 7 | |a Cation Transport Proteins |2 NLM | |
| 650 | 7 | |a CNNM2 protein, human |2 NLM | |
| 700 | 1 | |a Franken, Gijs A C |e verfasserin |4 aut | |
| 700 | 1 | |a de Las Heras, Javier |e verfasserin |4 aut | |
| 700 | 1 | |a Madariaga, Leire |e verfasserin |4 aut | |
| 700 | 1 | |a Barakat, Tahsin Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Oostenbrink, Rianne |e verfasserin |4 aut | |
| 700 | 1 | |a van Slegtenhorst, Marjon |e verfasserin |4 aut | |
| 700 | 1 | |a Perdomo-Ramírez, Ana |e verfasserin |4 aut | |
| 700 | 1 | |a Claverie-Martín, Félix |e verfasserin |4 aut | |
| 700 | 1 | |a van Eerde, Albertien M |e verfasserin |4 aut | |
| 700 | 1 | |a Vargas-Poussou, Rosa |e verfasserin |4 aut | |
| 700 | 1 | |a Dubourg, Laurence Derain |e verfasserin |4 aut | |
| 700 | 1 | |a González-Recio, Irene |e verfasserin |4 aut | |
| 700 | 1 | |a Martínez-Cruz, Luis Alfonso |e verfasserin |4 aut | |
| 700 | 1 | |a de Baaij, Jeroen H F |e verfasserin |4 aut | |
| 700 | 1 | |a Hoenderop, Joost G J |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Scientific reports |d 2011 |g 14(2024), 1 vom: 22. März, Seite 6917 |w (DE-627)NLM215703936 |x 2045-2322 |7 nnns |
| 773 | 1 | 8 | |g volume:14 |g year:2024 |g number:1 |g day:22 |g month:03 |g pages:6917 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41598-024-57061-7 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 14 |j 2024 |e 1 |b 22 |c 03 |h 6917 | ||