Chromosome 17q12 microdeletions but not intragenic HNF1B mutations link developmental kidney disease and psychiatric disorder.

2.50
Hdl Handle:
http://hdl.handle.net/11287/611708
Title:
Chromosome 17q12 microdeletions but not intragenic HNF1B mutations link developmental kidney disease and psychiatric disorder.
Authors:
Clissold, Rhian L. ( 0000-0002-3090-3492 ) ; Shaw-Smith, Charles; Turnpenny, Peter D.; Bunce, Benjamin; Bockenhauer, D.; Kerecuk, L.; Waller, S.; Bowman, Pamela; Ford, T.; Ellard, Sian ( 0000-0002-7620-5526 ) ; Hattersley, Andrew T.; Bingham, Coralie
Abstract:
Heterozygous mutations of the HNF1B gene are the commonest known monogenic cause of developmental kidney disease. Half of patients have a deletion (approximately 1.3 Mb) of chromosome 17q12, encompassing HNF1B plus 14 additional genes. This 17q12 deletion has been linked with an increased risk of neurodevelopmental disorders, such as autism. Here we compared the neurodevelopmental phenotype of 38 patients with HNF1B-associated renal disease due to an intragenic mutation in 18 patients or due to 17q12 deletion in 20 patients to determine whether haploinsufficiency of HNF1B is responsible for the neurodevelopmental phenotype. Significantly, brief behavioral screening in children with the deletion showed high levels of psychopathology and its impact. Eight individuals (40%) with a deletion had a clinical diagnosis of a neurodevelopmental disorder compared to none with an intragenic mutation. The 17q12 deletions were also associated with more autistic traits. Two independent clinical geneticists were able to predict the presence of a deletion with a sensitivity of 83% and specificity of 79% when assessing facial dysmorphic features as a whole. Thus, the 17q12 deletions but not HNF1B intragenic mutations are associated with neurodevelopmental disorders. Hence, the HNF1B gene is not involved in the neurodevelopmental phenotype of these patients. Nephrologists need to be aware of this association to ensure appropriate referral to psychiatric services.
Citation:
Chromosome 17q12 microdeletions but not intragenic HNF1B mutations link developmental kidney disease and psychiatric disorder. 2016 Jul;90(1):203-11. Kidney Int.
Publisher:
Elsevier
Journal:
Kidney international
Issue Date:
24-May-2016
URI:
http://hdl.handle.net/11287/611708
DOI:
10.1016/j.kint.2016.03.027
PubMed ID:
27234567
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S0085-2538(16)30115-6
Note:
This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.
Type:
Journal Article
Language:
en
ISSN:
1523-1755
Appears in Collections:
Exeter Kidney Unit (Renal); Diabetes/Endocrine Services; Clinical Genetics (Peninsula Genetics); Molecular Genetics; Honorary contracts publications; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorClissold, Rhian L.en
dc.contributor.authorShaw-Smith, Charlesen
dc.contributor.authorTurnpenny, Peter D.en
dc.contributor.authorBunce, Benjaminen
dc.contributor.authorBockenhauer, D.en
dc.contributor.authorKerecuk, L.en
dc.contributor.authorWaller, S.en
dc.contributor.authorBowman, Pamelaen
dc.contributor.authorFord, T.en
dc.contributor.authorEllard, Sianen
dc.contributor.authorHattersley, Andrew T.en
dc.contributor.authorBingham, Coralieen
dc.date.accessioned2016-06-03T11:44:26Z-
dc.date.available2016-06-03T11:44:26Z-
dc.date.issued2016-05-24-
dc.identifier.citationChromosome 17q12 microdeletions but not intragenic HNF1B mutations link developmental kidney disease and psychiatric disorder. 2016 Jul;90(1):203-11. Kidney Int.en
dc.identifier.issn1523-1755-
dc.identifier.pmid27234567-
dc.identifier.doi10.1016/j.kint.2016.03.027-
dc.identifier.urihttp://hdl.handle.net/11287/611708-
dc.description.abstractHeterozygous mutations of the HNF1B gene are the commonest known monogenic cause of developmental kidney disease. Half of patients have a deletion (approximately 1.3 Mb) of chromosome 17q12, encompassing HNF1B plus 14 additional genes. This 17q12 deletion has been linked with an increased risk of neurodevelopmental disorders, such as autism. Here we compared the neurodevelopmental phenotype of 38 patients with HNF1B-associated renal disease due to an intragenic mutation in 18 patients or due to 17q12 deletion in 20 patients to determine whether haploinsufficiency of HNF1B is responsible for the neurodevelopmental phenotype. Significantly, brief behavioral screening in children with the deletion showed high levels of psychopathology and its impact. Eight individuals (40%) with a deletion had a clinical diagnosis of a neurodevelopmental disorder compared to none with an intragenic mutation. The 17q12 deletions were also associated with more autistic traits. Two independent clinical geneticists were able to predict the presence of a deletion with a sensitivity of 83% and specificity of 79% when assessing facial dysmorphic features as a whole. Thus, the 17q12 deletions but not HNF1B intragenic mutations are associated with neurodevelopmental disorders. Hence, the HNF1B gene is not involved in the neurodevelopmental phenotype of these patients. Nephrologists need to be aware of this association to ensure appropriate referral to psychiatric services.en
dc.languageENG-
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0085-2538(16)30115-6en
dc.rightsArchived with thanks to Kidney International. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).en
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subjectWessex Classification Subject Headings::Urology::Nephrology/Renal medicineen
dc.titleChromosome 17q12 microdeletions but not intragenic HNF1B mutations link developmental kidney disease and psychiatric disorder.en
dc.typeJournal Articleen
dc.identifier.journalKidney internationalen
dc.description.noteThis article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.en
dc.description.fundingMedical Research Councilen
dc.type.versionIn press (epub ahead of print)en

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