Diagnostic Genetic Testing for Monogenic Diabetes and Congenital Hyperinsulinemia

Recommendations for Diagnostic Genetic Testing in Epilepsies

Neuropediatrics ◽

10.1055/s-0037-1603006 ◽

2017 ◽

Vol 48 (S 01) ◽

pp. S1-S45

Author(s):

S. von Spiczak ◽

K.-M. Klein ◽

G. Kluger ◽

J. Lemke ◽

B. Neubauer ◽

...

Keyword(s):

Genetic Testing ◽

Diagnostic Genetic Testing

Download Full-text

Frequency and characterization of mutations in genes in a large cohort of patients referred to MODY registry

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0501 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Emily Breidbart ◽

Liyong Deng ◽

Patricia Lanzano ◽

Xiao Fan ◽

Jiancheng Guo ◽

...

Keyword(s):

Genetic Testing ◽

Exome Sequencing ◽

Large Scale ◽

Age Of Onset ◽

Family Members ◽

Ethnically Diverse ◽

Monogenic Diabetes ◽

Diabetes Diagnosis ◽

Pathogenic Variants ◽

Atypical Diabetes

Abstract Objectives There have been few large-scale studies utilizing exome sequencing for genetically undiagnosed maturity onset diabetes of the young (MODY), a monogenic form of diabetes that is under-recognized. We describe a cohort of 160 individuals with suspected monogenic diabetes who were genetically assessed for mutations in genes known to cause MODY. Methods We used a tiered testing approach focusing initially on GCK and HNF1A and then expanding to exome sequencing for those individuals without identified mutations in GCK or HNF1A. The average age of onset of hyperglycemia or diabetes diagnosis was 19 years (median 14 years) with an average HbA1C of 7.1%. Results Sixty (37.5%) probands had heterozygous likely pathogenic/pathogenic variants in one of the MODY genes, 90% of which were in GCK or HNF1A. Less frequently, mutations were identified in PDX1, HNF4A, HNF1B, and KCNJ11. For those probands with available family members, 100% of the variants segregated with diabetes in the family. Cascade genetic testing in families identified 75 additional family members with a familial MODY mutation. Conclusions Our study is one of the largest and most ethnically diverse studies using exome sequencing to assess MODY genes. Tiered testing is an effective strategy to genetically diagnose atypical diabetes, and familial cascade genetic testing identified on average one additional family member with monogenic diabetes for each mutation identified in a proband.

Download Full-text

Rates of diagnostic genetic testing in a tertiary ocular genetics clinic

Ophthalmic Genetics ◽

10.1080/13816810.2020.1759107 ◽

2020 ◽

Vol 41 (3) ◽

pp. 271-274 ◽

Cited By ~ 1

Author(s):

R. Scott Lowery ◽

John R. Dehnel ◽

G. Bradley Schaefer ◽

Sami H. Uwaydat

Keyword(s):

Genetic Testing ◽

Diagnostic Genetic Testing

Download Full-text

Diagnostic genetic testing for Huntington's disease

Practical Neurology ◽

10.1136/practneurol-2013-000790 ◽

2014 ◽

Vol 15 (1) ◽

pp. 80-84 ◽

Cited By ~ 23

Author(s):

David Craufurd ◽

Rhona MacLeod ◽

Marina Frontali ◽

Oliver Quarrell ◽

Emilia K Bijlsma ◽

...

Keyword(s):

Genetic Testing ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Diagnostic Genetic Testing

Download Full-text

Predictive and Diagnostic Genetic Testing in Psychiatry

Psychiatric Clinics of North America ◽

10.1016/j.psc.2009.10.001 ◽

2010 ◽

Vol 33 (1) ◽

pp. 225-243 ◽

Cited By ~ 17

Author(s):

Philip B. Mitchell ◽

Bettina Meiser ◽

Alex Wilde ◽

Janice Fullerton ◽

Jennifer Donald ◽

...

Keyword(s):

Genetic Testing ◽

Diagnostic Genetic Testing

Download Full-text

Syndromic Monogenic Diabetes Genes Should be Tested in Patients With a Clinical Suspicion of MODY

10.2337/figshare.17000605 ◽

2021 ◽

Author(s):

Kevin Colclough ◽

Sian Ellard ◽

Andrew Hattersley ◽

Kashyap Patel

Keyword(s):

Genetic Testing ◽

Clinical Features ◽

Clinical Care ◽

Monogenic Diabetes ◽

Clinical Suspicion ◽

Genetic Syndrome ◽

Routine Clinical Care ◽

Common Causes ◽

Diabetes Gene ◽

Diabetes Patients

At present, outside of infancy, genetic testing for monogenic diabetes is typically for mutations in MODY genes that predominantly result in isolated diabetes. Monogenic diabetes syndromes are usually only tested when this is supported by specific syndromic clinical features. It is not known how frequently patients with suspected MODY have a mutation in a monogenic syndromic diabetes gene and thus missed by present testing regimes. We performed genetic testing of 27 monogenic diabetes genes (including 18 associated with syndromic diabetes) for 1280 patients with a clinical suspicion of MODY from routine clinical care that were not suspected of having monogenic syndromic diabetes. We confirmed monogenic diabetes in 297 (23%) patients. Mutations in 7 different syndromic diabetes genes accounted for 19% (95%CI 15-24%) of all monogenic diabetes. The mitochondrial m.3243A>G and mutations in HNF1B were responsible for the majority of mutations in syndromic diabetes genes. They were also the 4th and 5th most common causes of monogenic diabetes overall. These patients lacked typical features and their diabetes phenotypes overlapped with non-syndromic monogenic diabetes patients. Syndromic monogenic diabetes genes (particularly m.3243A>G and HNF1B) should be routinely tested in patients with suspected MODY that do not have typical features of a genetic syndrome.

Download Full-text

Is it acceptable to contact an anonymous egg donor to facilitate diagnostic genetic testing for the donor-conceived child?

Journal of Medical Ethics ◽

10.1136/medethics-2018-105322 ◽

2019 ◽

Vol 45 (6) ◽

pp. 357-360 ◽

Cited By ~ 4

Author(s):

Rachel Horton ◽

Benjamin Bell ◽

Angela Fenwick ◽

Anneke M Lucassen

Keyword(s):

Genetic Testing ◽

Dynamic Process ◽

Rapid Evolution ◽

Future Research ◽

Clinical Genetic ◽

Consent Forms ◽

Clinical Genetic Testing ◽

Egg Donor ◽

Diagnostic Genetic Testing ◽

Do So

We discuss a case where medically optimal investigations of health problems in a donor-conceived child would require their egg donor to participate in genetic testing. We argue that it would be justified to contact the egg donor to ask whether she would consider this, despite her indicating on a historical consent form that she did not wish to take part in future research and that she did not wish to be informed if she was found to be a carrier of a ‘harmful inherited condition’. We suggest that we cannot conjecture what her current answer might be if, by participating in clinical genetic testing, she might help reach a diagnosis for the donor-conceived child. At the point that she made choices regarding future contact, it was not yet evident that the interests of the donor-conceived child might be compromised by her answers, as it was not foreseen that the egg donor’s genome might one day have the potential to enable diagnosis for this child. Fertility consent forms tend to be conceptualised as representing incontrovertible historical boundaries, but we argue that rapid evolution in genomic practice means that consent in such cases is better seen as an ongoing and dynamic process. It cannot be possible to compel the donor to aid in the diagnosis of the donor-conceived child, but she should be given the opportunity to do so.

Download Full-text