Inhibition of G-protein signaling in cardiac dysfunction of Intellectual Developmental Disorder with Cardiac Arrhythmia (IDDCA) syndrome

IDDCA (MIM #617173) is an ultra-rare autosomal recessive disorder caused by mutations in GNB5 gene. Genotype-phenotype correlation shows that homozygous or compound heterozygous missense variants are associated with an attenuated phenotype with mild intellectual disability (ID) and sinus node dysfunction, while homozygous null alleles cause severe ID with absent speech, epileptic encephalopathy, hypotonia and sinus node dysfunction. In this study, we investigated the cardiac dysfunction in a Gnb5 knock-out mouse models of IDDCA for the first time and identified, in parallel, additional affected individuals harbouring novel pathogenic variants. Using blockade or stimulation of the parasympathetic and sympathetic systems we propose a mechanism underlying cardiac dysfunction in patients, namely impaired parasympathetic control of the heart.  (By Pasquelena De Nittis, https://jmg.bmj.com/content/early/2020/11/09/jmedgenet-2020-107015 )

(Visited 217 times, 1 visits today)