Article Text

other Versions

PDF
Idiopathic Restrictive Cardiomyopathy in Children is Caused by Mutations in Cardiac Sarcomere Protein Genes
  1. Juan Pablo Kaski (j.kaski{at}ucl.ac.uk)
  1. Institute of Child Health, United Kingdom
    1. Petros Syrris (p.syrris{at}ucl.ac.uk)
    1. University College London, United Kingdom
      1. Michael Burch (burchm{at}gosh.nhs.uk)
      1. Great Ormond Street Hospital, United Kingdom
        1. Maria-Teresa Tome-Esteban (maite.tome{at}uclh.nhs.uk)
        1. Great Ormond Street Hospital, United Kingdom
          1. Matthew Fenton (fentom{at}gosh.nhs.uk)
          1. Great Ormond Street Hospital, United Kingdom
            1. Michael Christiansen (mic{at}ssi.dk)
            1. Statens Serum Institut, Denmark
              1. Paal S Andersen (psa{at}ssi.dk)
              1. Statens Serum Institut, Denmark
                1. Neil Sebire (sebirn{at}gosh.nhs.uk)
                1. Great Ormond Street Hospital, United Kingdom
                  1. Michael Ashworth (ashwom{at}gosh.nhs.uk)
                  1. Great Ormond Street Hospital, United Kingdom
                    1. John E Deanfield (j.deanfield{at}ich.ucl.ac.uk)
                    1. Great Ormond Street Hospital, United Kingdom
                      1. William J McKenna (william.mckenna{at}uclh.nhs.uk)
                      1. Great Ormond Street Hospital, United Kingdom
                        1. Perry M Elliott (pelliott{at}doctors.org.uk)
                        1. Great Ormond Street Hospital, United Kingdom

                          Abstract

                          Aim To determine the prevalence of sarcomere protein gene mutations in children with idiopathic restrictive cardiomyopathy (RCM).

                          Background RCM is rare in childhood, but has a grave prognosis. The cause of disease in most cases is unknown.

                          Methods Twelve patients (9 females, mean age 5.1 years) with idiopathic RCM referred between 1991 and August 2006 underwent detailed clinical and genetic evaluation. Nine had received cardiac transplants at the time of the study. The entire coding sequences of the genes encoding eight cardiac sarcomere proteins and desmin were screened for mutations. Familial evaluation was performed on first-degree relatives.

                          Results Four patients (33%) had a family history of cardiomyopathy: RCM (n=2); dilated cardiomyopathy (n=1); and left ventricular noncompaction (n=1). Sarcomere protein gene mutations were identified in four patients (33%): 2 in the cardiac troponin I gene (TNNI3) and 1 each in the troponin T (TNNT2) and α-cardiac actin (ACTC) genes. Two were de novo mutations and 3 were novel mutations. All mutations occurred in functionally important and conserved regions of the genes.

                          Conclusions Sarcomere protein gene mutations are an important cause of idiopathic RCM in childhood. We describe the first mutation in ACTC in familial RCM. The identification of RCM in a child should prompt consideration of sarcomere protein disease as a possible cause and warrants clinical evaluation of the family.

                          Statistics from Altmetric.com

                          Request permissions

                          If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.