Dataset Information

An ADAMTS3 missense variant is associated with Norwich Terrier upper airway syndrome.

ABSTRACT: In flat-faced dog breeds, air resistance caused by skull conformation is believed to be a major determinant of Brachycephalic Obstructive Airway Syndrome (BOAS). The clinical presentation of BOAS is heterogeneous, suggesting determinants independent of skull conformation contribute to airway disease. Norwich Terriers, a mesocephalic breed, are predisposed to Upper Airway Syndrome (UAS), a disease whose pathological features overlap with BOAS. Our health screening clinic examined and scored the airways of 401 Norwich terriers by laryngoscopy. Genome-wide association analyses of UAS-related pathologies revealed a genetic association on canine chromosome 13 (rs9043975, p = 7.79x10-16). Whole genome resequencing was used to identify causal variant(s) within a 414 kb critical interval. This approach highlighted an error in the CanFam3.1 dog assembly, which when resolved, led to the discovery of a c.2786G>A missense variant in exon 20 of the positional candidate gene, ADAM metallopeptidase with thrombospondin type 1 motif 3 (ADAMTS3). In addition to segregating with UAS amongst Norwich Terriers, the ADAMTS3 c.2786G>A risk allele frequency was enriched among the BOAS-susceptible French and (English) Bulldogs. Previous studies indicate that ADAMTS3 loss of function results in lymphoedema. Our results suggest a new paradigm in the understanding of canine upper airway disease aetiology: airway oedema caused by disruption of ADAMTS3 predisposes dogs to respiratory obstruction. These findings will enhance breeding practices and could refine the prognostics of surgical interventions that are often used to treat airway obstruction.

SUBMITTER: Marchant TW

PROVIDER: S-EPMC6521993 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An ADAMTS3 missense variant is associated with Norwich Terrier upper airway syndrome.

Marchant Thomas W TW Dietschi Elisabeth E Rytz Ulrich U Schawalder Peter P Jagannathan Vidhya V Hadji Rasouliha Sheida S Gurtner Corinne C Waldvogel Andreas S AS Harrington Ronan S RS Drögemüller Michaela M Kidd Jeffrey J Ostrander Elaine A EA Warr Amanda A Watson Mick M Argyle David D Ter Haar Gert G Clements Dylan N DN Leeb Tosso T Schoenebeck Jeffrey J JJ

PLoS genetics 20190516 5

In flat-faced dog breeds, air resistance caused by skull conformation is believed to be a major determinant of Brachycephalic Obstructive Airway Syndrome (BOAS). The clinical presentation of BOAS is heterogeneous, suggesting determinants independent of skull conformation contribute to airway disease. Norwich Terriers, a mesocephalic breed, are predisposed to Upper Airway Syndrome (UAS), a disease whose pathological features overlap with BOAS. Our health screening clinic examined and scored the a ...[more]

PMID: 31095560

Similar Datasets

Project description:IntroductionStudies that assess the upper airways in sleep-related breathing disorders have been performed only in patients with obstructive sleep apnea syndrome who seek medical attention. Therefore, in addition to the need for population studies, there are no data on the orofacial-cervical physical examination in subjects with upper airway resistance syndrome.ObjectivesTo compare the orofacial-cervical examination between volunteers with upper airway resistance syndrome and without sleep-related breathing disorders.MethodsThrough questionnaires, physical measurements, polysomnography, and otorhinolaryngological evaluation, this study compared the orofacial-cervical physical examination, through a systematic analysis of the facial skeleton, mouth, throat, and nose, between volunteers with upper airway resistance syndrome and volunteers without sleep-related breathing disorders in a representative sample of the adult population of the city of São Paulo.ResultsThere were 1042 volunteers evaluated; 49 subjects (5%) were excluded as they did not undergo otorhinolaryngological evaluation, 381 (36%) had apnea-hypopnea index>5 events/hour, and 131 (13%) had oxyhemoglobin saturation<90%. Among the remaining 481 subjects (46%), 30 (3%) met the criteria for the upper airway resistance syndrome definition and 53 (5%) met the control group criteria. At the clinical evaluation of nasal symptoms, the upper airway resistance syndrome group had more oropharyngeal dryness (17% vs. 29.6%; p=0.025) and septal deviation grades 1-3 (49.1% vs. 57.7%; p=0.025) when compared to controls. In the logistic regression model, it was found that individuals from the upper airway resistance syndrome group had 15.6-fold higher chance of having nose alterations, 11.2-fold higher chance of being hypertensive, and 7.6-fold higher chance of complaining of oropharyngeal dryness when compared to the control group.ConclusionSystematic evaluation of the facial skeleton, mouth, throat, and nose, between volunteers with upper airway resistance syndrome and volunteers without sleep-related breathing disorders, showed that the presence of upper airway resistance syndrome is mainly associated with nasal alterations and oropharyngeal dryness, in addition to the risk of hypertension, regardless of gender and obesity.

Dataset Information

An ADAMTS3 missense variant is associated with Norwich Terrier upper airway syndrome.

Publications

An ADAMTS3 missense variant is associated with Norwich Terrier upper airway syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets