Two novel presentations of KCNMA1-related pathology--Expanding the clinical phenotype of a rare channelopathy.
Adolescent
Alleles
Amino Acid Substitution
Channelopathies
/ diagnosis
Child
Child, Preschool
Genetic Association Studies
/ methods
Genetic Predisposition to Disease
Humans
Infant
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
/ genetics
Male
Mutation
Neuroimaging
Phenotype
Tomography, X-Ray Computed
Ultrasonography
Exome Sequencing
Young Adult
KCNMA1 loss-of-function
Liang-Wang syndrome
channelopathy
thoracic aortic aneurysm
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
19
05
2021
received:
24
11
2020
accepted:
13
08
2021
pubmed:
10
9
2021
medline:
23
3
2022
entrez:
9
9
2021
Statut:
ppublish
Résumé
KCNMA1 mutations have recently been associated with a wide range of dysmorphological, gastro-intestinal, cardiovascular, and neurological manifestations. Whole exome sequencing was performed in order to identify the underlying pathogenic mutation in two cases presenting with diverse phenotypical manifestations that did not fit into well-known clinical entities. In an 8-year-old boy presenting with severe aortic dilatation, facial dysmorphism, and overgrowth at birth a de novo p.Gly375Arg KCNMA1 mutation was identified which has been reported previously in association with gingival hypertrophy, aortic dilatation, and developmental delay. Additionally, in a 30-week-old fetus with severe growth retardation and duodenal atresia a de novo p.Pro805Leu KCNMA1 mutation was identified. The latter has also been reported before in a boy with severe neurological manifestations, including speech delay, developmental delay, and cerebellar dysfunction. The current report presents the first antenatal presentation of a pathogenic KCNMA1 mutation and confirms the specific association of the p.Gly375Arg variant with early onset aortic root dilatation, gingival hypertrophy, and neonatal overgrowth.
Sections du résumé
BACKGROUND
KCNMA1 mutations have recently been associated with a wide range of dysmorphological, gastro-intestinal, cardiovascular, and neurological manifestations.
METHODS
Whole exome sequencing was performed in order to identify the underlying pathogenic mutation in two cases presenting with diverse phenotypical manifestations that did not fit into well-known clinical entities.
RESULTS
In an 8-year-old boy presenting with severe aortic dilatation, facial dysmorphism, and overgrowth at birth a de novo p.Gly375Arg KCNMA1 mutation was identified which has been reported previously in association with gingival hypertrophy, aortic dilatation, and developmental delay. Additionally, in a 30-week-old fetus with severe growth retardation and duodenal atresia a de novo p.Pro805Leu KCNMA1 mutation was identified. The latter has also been reported before in a boy with severe neurological manifestations, including speech delay, developmental delay, and cerebellar dysfunction.
CONCLUSION
The current report presents the first antenatal presentation of a pathogenic KCNMA1 mutation and confirms the specific association of the p.Gly375Arg variant with early onset aortic root dilatation, gingival hypertrophy, and neonatal overgrowth.
Identifiants
pubmed: 34499417
doi: 10.1002/mgg3.1797
pmc: PMC8580096
doi:
Substances chimiques
KCNMA1 protein, human
0
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1797Informations de copyright
© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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