dc.contributor.author | Laver, TW | |
dc.contributor.author | Wakeling, M | |
dc.contributor.author | Hua, JHY | |
dc.contributor.author | Houghton, J | |
dc.contributor.author | Hussain, K | |
dc.contributor.author | Ellard, S | |
dc.contributor.author | Flanagan, S | |
dc.date.accessioned | 2018-09-24T12:44:28Z | |
dc.date.issued | 2018-08-23 | |
dc.description.abstract | Objective
Hyperinsulinaemic hypoglycaemia (HH) can occur in isolation or more rarely feature as part of a syndrome. Screening for mutations in the “syndromic” HH genes is guided by phenotype with genetic testing used to confirm the clinical diagnosis. As HH can be the presenting feature of a syndrome, it is possible that mutations will be missed as these genes are not routinely screened in all newly diagnosed individuals. We investigated the frequency of pathogenic variants in syndromic genes in infants with HH who had not been clinically diagnosed with a syndromic disorder at referral for genetic testing.
Design
We used genome sequencing data to assess the prevalence of mutations in syndromic HH genes in an international cohort of patients with HH of unknown genetic cause.
Patients
We undertook genome sequencing in 82 infants with HH without a clinical diagnosis of a known syndrome at referral for genetic testing.
Measurements
Within this cohort, we searched for the genetic aetiologies causing 20 different syndromes where HH had been reported as a feature.
Results
We identified a pathogenic KMT2D variant in a patient with HH diagnosed at birth, confirming a genetic diagnosis of Kabuki syndrome. Clinical data received following the identification of the mutation highlighted additional features consistent with the genetic diagnosis. Pathogenic variants were not identified in the remainder of the cohort.
Conclusions
Pathogenic variants in the syndromic HH genes are rare; thus, routine testing of these genes by molecular genetics laboratories is unlikely to be justified in patients without syndromic phenotypes. | en_GB |
dc.description.sponsorship | SE is a Wellcome Trust Senior Investigator (grant number WT098395/Z/12/Z). SEF has a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number: 105636/Z/14/Z). | en_GB |
dc.identifier.citation | Published online 23 August 2018 | en_GB |
dc.identifier.doi | 10.1111/cen.13841 | |
dc.identifier.uri | http://hdl.handle.net/10871/34092 | |
dc.language.iso | en | en_GB |
dc.publisher | Wiley / Society for Endocrinology | en_GB |
dc.rights | © 2018 The Authors Clinical Endocrinology Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | en_GB |
dc.subject | genetic screening | en_GB |
dc.subject | hyperinsulinaemia hypoglycaemia of infancy | en_GB |
dc.subject | medical genetics | en_GB |
dc.subject | molecular diagnostics | en_GB |
dc.subject | mutation | en_GB |
dc.subject | neonatal hyperinsulinism | en_GB |
dc.subject | syndrome | en_GB |
dc.title | Comprehensive screening shows that mutations in the known syndromic genes are rare in infants presenting with hyperinsulinaemic hypoglycaemia | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2018-09-24T12:44:28Z | |
dc.identifier.issn | 0300-0664 | |
dc.description | This is the final version of the article. Available from Wiley via the DOI in this record. | en_GB |
dc.identifier.journal | Clinical Endocrinology | en_GB |