Recessively Inherited Lrba Mutations Cause Autoimmunity Presenting as Neonatal Diabetes.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620366
Title:
Recessively Inherited Lrba Mutations Cause Autoimmunity Presenting as Neonatal Diabetes.
Authors:
Johnson, M. B.; De Franco, E.; Lango-Allen, H.; Al Senani, A.; Elbarbary, N.; Siklar, Z.; Berberoglu, M.; Imane, Z.; Haghighi, A.; Ullah, I.; Alyaarubi, S.; Gardner, D.; Ellard, Sian ( 0000-0002-7620-5526 ) ; Hattersley, Andrew T.; Flanagan, S. E.
Abstract:
Young-onset autoimmune diabetes associated with additional autoimmunity usually reflects a polygenic predisposition but rare cases result from monogenic autoimmunity. Diagnosing monogenic autoimmunity is crucial for patients' prognosis and clinical management. We sought to identify novel genetic causes of autoimmunity presenting with neonatal diabetes (NDM; diagnosis <6 months).We performed exome sequencing in a patient with NDM and autoimmune lymphoproliferative syndrome and his unrelated, unaffected parents and identified compound heterozygous null mutations in LRBA Biallelic LRBA mutations cause Common Variable Immunodeficiency-8, however NDM has not been confirmed in this disorder. We sequenced LRBA in 169 additional patients with diabetes diagnosed <1 year without mutations in the 24 known NDM genes. We identified recessive null mutations in 8 additional probands, of which 3 had NDM (<6 months). Diabetes was the presenting feature in 6 of 9 probands. Six of 17 (35%) patients both born to consanguineous parents and with additional early-onset autoimmunity had recessive LRBA mutations.LRBA testing should be considered in patients with diabetes diagnosed <12 months, particularly if they have additional autoimmunity or are born to consanguineous parents. A genetic diagnosis is important as it can enable personalized therapy with abatacept, a CTLA4 mimetic, and inform genetic counselling.
Citation:
Recessively Inherited Lrba Mutations Cause Autoimmunity Presenting as Neonatal Diabetes. 2017 Diabetes
Publisher:
American Diabetes Association
Journal:
Diabetes
Issue Date:
4-May-2017
URI:
http://hdl.handle.net/11287/620366
DOI:
10.2337/db17-0040
PubMed ID:
28473463
Additional Links:
http://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=28473463
Type:
Journal Article
Language:
en
ISSN:
1939-327X
Appears in Collections:
Diabetes/Endocrine Services; Molecular Genetics; 2017 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorJohnson, M. B.en
dc.contributor.authorDe Franco, E.en
dc.contributor.authorLango-Allen, H.en
dc.contributor.authorAl Senani, A.en
dc.contributor.authorElbarbary, N.en
dc.contributor.authorSiklar, Z.en
dc.contributor.authorBerberoglu, M.en
dc.contributor.authorImane, Z.en
dc.contributor.authorHaghighi, A.en
dc.contributor.authorUllah, I.en
dc.contributor.authorAlyaarubi, S.en
dc.contributor.authorGardner, D.en
dc.contributor.authorEllard, Sianen
dc.contributor.authorHattersley, Andrew T.en
dc.contributor.authorFlanagan, S. E.en
dc.date.accessioned2017-07-20T12:54:20Z-
dc.date.available2017-07-20T12:54:20Z-
dc.date.issued2017-05-04-
dc.identifier.citationRecessively Inherited Lrba Mutations Cause Autoimmunity Presenting as Neonatal Diabetes. 2017 Diabetesen
dc.identifier.issn1939-327X-
dc.identifier.pmid28473463-
dc.identifier.doi10.2337/db17-0040-
dc.identifier.urihttp://hdl.handle.net/11287/620366-
dc.description.abstractYoung-onset autoimmune diabetes associated with additional autoimmunity usually reflects a polygenic predisposition but rare cases result from monogenic autoimmunity. Diagnosing monogenic autoimmunity is crucial for patients' prognosis and clinical management. We sought to identify novel genetic causes of autoimmunity presenting with neonatal diabetes (NDM; diagnosis <6 months).We performed exome sequencing in a patient with NDM and autoimmune lymphoproliferative syndrome and his unrelated, unaffected parents and identified compound heterozygous null mutations in LRBA Biallelic LRBA mutations cause Common Variable Immunodeficiency-8, however NDM has not been confirmed in this disorder. We sequenced LRBA in 169 additional patients with diabetes diagnosed <1 year without mutations in the 24 known NDM genes. We identified recessive null mutations in 8 additional probands, of which 3 had NDM (<6 months). Diabetes was the presenting feature in 6 of 9 probands. Six of 17 (35%) patients both born to consanguineous parents and with additional early-onset autoimmunity had recessive LRBA mutations.LRBA testing should be considered in patients with diabetes diagnosed <12 months, particularly if they have additional autoimmunity or are born to consanguineous parents. A genetic diagnosis is important as it can enable personalized therapy with abatacept, a CTLA4 mimetic, and inform genetic counselling.en
dc.language.isoenen
dc.publisherAmerican Diabetes Associationen
dc.relation.urlhttp://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=28473463en
dc.rightsArchived with thanks to Diabetesen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subjectWessex Classification Subject Headings::Endocrinology::Diabetesen
dc.titleRecessively Inherited Lrba Mutations Cause Autoimmunity Presenting as Neonatal Diabetes.en
dc.typeJournal Articleen
dc.identifier.journalDiabetesen
dc.type.versionIn press (epub ahead of print)en

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