Kilquist syndrome: A novel syndromic hearing loss disorder caused by homozygous deletion of SLC12A2.
NKCC1
absent salivation
cystic fibrosis
gut malrotation
uniparental isodisomy
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
22
07
2018
revised:
22
01
2019
accepted:
07
02
2019
pubmed:
12
2
2019
medline:
10
3
2020
entrez:
12
2
2019
Statut:
ppublish
Résumé
Syndromic sensorineural hearing loss is multigenic and associated with malformations of the ear and other organ systems. Herein we describe a child admitted to the NIH Undiagnosed Diseases Program with global developmental delay, sensorineural hearing loss, gastrointestinal abnormalities, and absent salivation. Next-generation sequencing revealed a uniparental isodisomy in chromosome 5, and a 22 kb homozygous deletion in SLC12A2, which encodes for sodium, potassium, and chloride transporter in the basolateral membrane of secretory epithelia. Functional studies using patient-derived fibroblasts showed truncated SLC12A2 transcripts and markedly reduced protein abundance when compared with control. Loss of Slc12a2 in mice has been shown to lead to deafness, abnormal neuronal growth and migration, severe gastrointestinal abnormalities, and absent salivation. Together with the described phenotype of the Slc12a2-knockout mouse model, our results suggest that the absence of functional SLC12A2 causes a new genetic syndrome and is crucial for the development of auditory, neurologic, and gastrointestinal tissues.
Identifiants
pubmed: 30740830
doi: 10.1002/humu.23722
pmc: PMC6693334
mid: NIHMS1011904
doi:
Substances chimiques
SLC12A2 protein, human
0
Solute Carrier Family 12, Member 2
0
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
532-538Subventions
Organisme : NHGRI NIH HHS
ID : U01 HG007943
Pays : United States
Organisme : Intramural NIH HHS
ID : Z99 HG999999
Pays : United States
Organisme : National Human Genome Research Institute of the National Institutes of Health
ID : U01HG007943
Pays : International
Informations de copyright
© 2019 Wiley Periodicals, Inc.
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