Reclassification of diabetes aetiology in a family with multiple diabetes phenotypes
Background: Maturity-onset diabetes of the young (MODY) is uncommon; however, accurate diagnosis facilitates personalized management and informs prognosis in probands and relatives. Objective: The objective of the study was to highlight that the appropriate use of genetic and nongenetic investigatio...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Conference item |
| Published: |
Endocrine Society
2013
|
| _version_ | 1797054586780909568 |
|---|---|
| author | Kavvoura, F Raimondo, A Thanabalasingham, G Barrett, A Webster, A Mann, N Ellard, S Gloyn, A Owen, K |
| author_facet | Kavvoura, F Raimondo, A Thanabalasingham, G Barrett, A Webster, A Mann, N Ellard, S Gloyn, A Owen, K |
| author_sort | Kavvoura, F |
| collection | OXFORD |
| description | Background: Maturity-onset diabetes of the young (MODY) is uncommon; however, accurate diagnosis facilitates personalized management and informs prognosis in probands and relatives. Objective: The objective of the study was to highlight that the appropriate use of genetic and nongenetic investigations leads to the correct classification of diabetes etiology. Case Discussion: A 30-year-old European female was diagnosed with insulin-treated gestational diabetes. She discontinued insulin after delivery; however, her fasting hyperglycemia persisted. β-Cell antibodies were negative and C-peptide was 0.79 nmol/L. Glucokinase (GCK)-MODY was suspected and confirmed by the identification of a GCK mutation (p.T206M). Methods: Systematic clinical and biochemical characterization and GCK mutational analysis were implemented to determine the diabetes etiology in five relatives. Functional characterization of GCK mutations was performed. Results: Identification of the p.T206M mutation in the proband's sister confirmed a diagnosis of GCKMODY. Her daughter was diagnosed at 16 weeks with permanent neonatal diabetes (PNDM). Mutation analysis identifiedtwoGCKmutations thatwereinherited in trans-p. [(R43P);(T206M)], confirming a diagnosis of GCK-PNDM. Both mutations were shown to be kinetically inactivating. The proband's mother, other sister, and daughter all had a clinical diagnosis of type 1 diabetes, confirmed by undetectable C-peptide levels and β-Cell antibody positivity. GCK mutations were not detected. Conclusions: Two previously misclassified family members were shown to have GCK-MODY, whereas another was shown to have GCK-PNDM. A diagnosis of type 1 diabetes was confirmed in three relatives. This family exemplifies the importance of careful phenotyping and systematic evaluation of relatives after discovering monogenic diabetes in an individual. © 2014 by the Endocrine Society. |
| first_indexed | 2024-03-06T18:59:18Z |
| format | Conference item |
| id | oxford-uuid:12f7d018-4d97-4b98-a9c0-37d685b9efbe |
| institution | University of Oxford |
| last_indexed | 2024-03-06T18:59:18Z |
| publishDate | 2013 |
| publisher | Endocrine Society |
| record_format | dspace |
| spelling | oxford-uuid:12f7d018-4d97-4b98-a9c0-37d685b9efbe2022-03-26T10:11:05ZReclassification of diabetes aetiology in a family with multiple diabetes phenotypesConference itemhttp://purl.org/coar/resource_type/c_5794uuid:12f7d018-4d97-4b98-a9c0-37d685b9efbeSymplectic Elements at OxfordEndocrine Society2013Kavvoura, FRaimondo, AThanabalasingham, GBarrett, AWebster, AMann, NEllard, SGloyn, AOwen, KBackground: Maturity-onset diabetes of the young (MODY) is uncommon; however, accurate diagnosis facilitates personalized management and informs prognosis in probands and relatives. Objective: The objective of the study was to highlight that the appropriate use of genetic and nongenetic investigations leads to the correct classification of diabetes etiology. Case Discussion: A 30-year-old European female was diagnosed with insulin-treated gestational diabetes. She discontinued insulin after delivery; however, her fasting hyperglycemia persisted. β-Cell antibodies were negative and C-peptide was 0.79 nmol/L. Glucokinase (GCK)-MODY was suspected and confirmed by the identification of a GCK mutation (p.T206M). Methods: Systematic clinical and biochemical characterization and GCK mutational analysis were implemented to determine the diabetes etiology in five relatives. Functional characterization of GCK mutations was performed. Results: Identification of the p.T206M mutation in the proband's sister confirmed a diagnosis of GCKMODY. Her daughter was diagnosed at 16 weeks with permanent neonatal diabetes (PNDM). Mutation analysis identifiedtwoGCKmutations thatwereinherited in trans-p. [(R43P);(T206M)], confirming a diagnosis of GCK-PNDM. Both mutations were shown to be kinetically inactivating. The proband's mother, other sister, and daughter all had a clinical diagnosis of type 1 diabetes, confirmed by undetectable C-peptide levels and β-Cell antibody positivity. GCK mutations were not detected. Conclusions: Two previously misclassified family members were shown to have GCK-MODY, whereas another was shown to have GCK-PNDM. A diagnosis of type 1 diabetes was confirmed in three relatives. This family exemplifies the importance of careful phenotyping and systematic evaluation of relatives after discovering monogenic diabetes in an individual. © 2014 by the Endocrine Society. |
| spellingShingle | Kavvoura, F Raimondo, A Thanabalasingham, G Barrett, A Webster, A Mann, N Ellard, S Gloyn, A Owen, K Reclassification of diabetes aetiology in a family with multiple diabetes phenotypes |
| title | Reclassification of diabetes aetiology in a family with multiple diabetes phenotypes |
| title_full | Reclassification of diabetes aetiology in a family with multiple diabetes phenotypes |
| title_fullStr | Reclassification of diabetes aetiology in a family with multiple diabetes phenotypes |
| title_full_unstemmed | Reclassification of diabetes aetiology in a family with multiple diabetes phenotypes |
| title_short | Reclassification of diabetes aetiology in a family with multiple diabetes phenotypes |
| title_sort | reclassification of diabetes aetiology in a family with multiple diabetes phenotypes |
| work_keys_str_mv | AT kavvouraf reclassificationofdiabetesaetiologyinafamilywithmultiplediabetesphenotypes AT raimondoa reclassificationofdiabetesaetiologyinafamilywithmultiplediabetesphenotypes AT thanabalasinghamg reclassificationofdiabetesaetiologyinafamilywithmultiplediabetesphenotypes AT barretta reclassificationofdiabetesaetiologyinafamilywithmultiplediabetesphenotypes AT webstera reclassificationofdiabetesaetiologyinafamilywithmultiplediabetesphenotypes AT mannn reclassificationofdiabetesaetiologyinafamilywithmultiplediabetesphenotypes AT ellards reclassificationofdiabetesaetiologyinafamilywithmultiplediabetesphenotypes AT gloyna reclassificationofdiabetesaetiologyinafamilywithmultiplediabetesphenotypes AT owenk reclassificationofdiabetesaetiologyinafamilywithmultiplediabetesphenotypes |