Molecular genetics & genomic medicine · 2021
Two novel presentations of KCNMA1-related pathology--Expanding the clinical phenotype of a rare channelopathy.
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Rodrigues Bento Jotte, Feben Candice, Kempers Marlies, van Rij Maartje, Woiski Mallory, Devriendt Koenraad, De Catte Luc, Baldewijns Marcella, Alaerts Maaike, Meester Josephina, Verstraeten Aline, Hendson Willy, Loeys Bart
Аннотация
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.
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.
Предметные рубрики MeSH
AdolescentAllelesAmino Acid SubstitutionChannelopathiesChildChild, PreschoolGenetic Association StudiesGenetic Predisposition to DiseaseHumansInfantLarge-Conductance Calcium-Activated Potassium Channel alpha SubunitsMaleMutationNeuroimagingPhenotypeTomography, X-Ray ComputedUltrasonographyExome SequencingYoung Adult