Novel Mutations in the TAZ Gene in Patients with Barth Syndrome

S Mazurová,J Zeman,J Augustínová,M Magner,H Hansíková,M Tesařová,V Tomek,H Houšťková,A Vondráčková,Tomáš Honzík

doi:10.14712/23362936.2014.16

Abstract

Barth syndrome is an X-linked recessive disorder that is caused by mutations in Taffazin gene (TAZ), leading to severe cardiolipin deficiency which results in respiratory chain dysfunction. Barth syndrome is characterized by cardiomyopathy, neutropenia, skeletal myopathy, growth deficiency and 3-methylglutaconic aciduria. In this paper, we present clinical, biochemical and molecular data of the first four Czech patients from four unrelated families diagnosed with this rare disease. The mean age of onset was 5.5 ± 3.8 months. One child suffered from sudden cardiac death at the age of 2 years, the age of living patients is between 3 and 13 years. Muscle hypotonia was present in all four patients; cardiomyopathy and growth retardation in three and neutropenia in two of them. Two patients manifested a dilated and one patient a hypertrophic cardiomyopathy. A characteristic laboratory abnormality was the intermittently increased excretion of 3-methylglutaconic acid. Three novel hemizygous mutations in the TAZ gene were found (c.584G>T; c.109+6T>C; c.86G>A). We conclude that Barth syndrome should be included in differential diagnosis of cardiomyopathy in childhood, especially in the cooccurrence of dilated cardiomyopathy and 3-methylglutaconic aciduria.

Highlights

Barth syndrome (BTHS) is an X-linked recessive disorder that is caused by mutations in the Taffazin gene (TAZ) at Xq28 (Bolhuis et al, 1991; Bione et al, 1996)
We focused on the three novel mutations found in the T AZ gene and cardiological findings in these patients with the aim of bringing proper attention to BTHS in differential diagnosis of dilated/hypertrophic CMP in children
Clinical and laboratory findings From 2007 to 2012, four male patients from four unrelated families were diagnosed with BTHS

Summary

Introduction

Barth syndrome (BTHS) is an X-linked recessive disorder that is caused by mutations in the Taffazin gene (TAZ) at Xq28 (Bolhuis et al, 1991; Bione et al, 1996). BTHS was first described by Barth et al in 1983 in an extended pedigree with dilated cardiomyopathy (CMP), skeletal myopathy and neutropenia. BTHS is characterized by growth failure and 3-methylglutaconic aciduria (3-MGA); note that 3-MGA is not specific to BTHS and is classified as 3-MGA type II (Kelley et al, 1991; Christodoulou et al, 1994). The estimated incidence of BTHS (according to www.barthsyndrome.org register) is 1 to 300,000–400,000 male births, but accurate incidence is not known and BTHS seems to be underdiagnosed

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