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Göteborgs universitets publikationer

Alpha-cardiac actin mutations produce atrial septal defects.

Författare och institution:
Hans Matsson (-); Jacqueline Eason (-); Carol S Bookwalter (-); Joakim Klar (-); Peter Gustavsson (-); Jan Sunnegårdh (Institutionen för kliniska vetenskaper, sektionen för kvinnors och barns hälsa); Henrik Enell (-); Anders Jonzon (-); Miikka Vikkula (-); Ilse Gutierrez (-); Javier Granados-Riveron (-); Mark Pope (-); Frances Bu'Lock (-); Jane Cox (-); Thelma E Robinson (-); Feifei Song (-); David J Brook (-); Steven Marston (-); Kathleen M Trybus (-); Niklas Dahl (-)
Publicerad i:
Human molecular genetics, 17 ( 2 ) s. 256-65
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Atrial septal defect (ASD) is one of the most frequent congenital heart defects (CHDs) with a variable phenotypic effect depending on the size of the septal shunt. We identified two pedigrees comprising 20 members segregating isolated autosomal dominant secundum ASD. By genetic mapping, we identified the gene-encoding alpha-cardiac actin (ACTC1), which is essential for cardiac contraction, as the likely candidate. A mutation screen of the coding regions of ACTC1 revealed a founder mutation predicting an M123V substitution in affected individuals of both pedigrees. Functional analysis of ACTC1 with an M123V substitution shows a reduced affinity for myosin, but with retained actomyosin motor properties. We also screened 408 sporadic patients with CHDs and identified a case with ASD and a 17-bp deletion in ACTC1 predicting a non-functional protein. Morpholino (MO) knockdown of ACTC1 in chick embryos produces delayed looping and reduced atrial septa, supporting a developmental role for this protein. The combined results indicate, for the first time, that ACTC1 mutations or reduced ACTC1 levels may lead to ASD without signs of cardiomyopathy.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper ->
Medicinsk genetik
Actins, chemistry, genetics, metabolism, Amino Acid Substitution, Animals, Chick Embryo, Child, Preschool, Female, Gene Deletion, Heart, embryology, Heart Septal Defects, Atrial, genetics, metabolism, Humans, Infant, Male, Mutagenesis, Site-Directed, Myosins, metabolism, Pedigree
Postens nummer:
Posten skapad:
2010-07-01 15:18
Posten ändrad:
2011-01-20 10:00

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