title: Barth syndrome associated with compound hemizygosity and heterozygosity of the TAZ and LDB3 genes.
abstract: Barth syndrome is an X-linked recessive disorder caused by the tafazzin (TAZ) gene mutations and includes dilated cardiomyopathy (DCM) with left ventricular non-compaction, neutropenia, skeletal myopathy, abnormal mitochondria and 3-methylglutaconic aciduria. Dilated cardiomyopathy with left ventricular non-compaction transmitted as an autosomal dominant condition has also been associated with LIM domain-binding 3 (LDB3) gene defects. We describe a family in which the 12-year-old proband had left ventricular non-compaction and DCM. His mother had five miscarriages, two other sons who died in infancy, and a healthy son and daughter. The proband showed left ventricular non-compaction-DCM, skeletal myopathy, recurrent oral aphthous ulcers and cyclic neutropenia. The DCM progressively improved with age; medical therapy was discontinued at 5 years of age. At present, left ventricular function is normal and arrhythmias are absent. Magnetic resonance imaging documented left ventricular non-compaction. However, oral aphthous ulcers and cyclic neutropenia have recurred. In the proband we identified two novel mutations, one of maternal origin in the TAZ gene (p.[Glu202ValfsX15]) and one of paternal origin in the LDB3 gene (p.[Thr350Ile]). The mother, brother and father are healthy; although the latter two show prominent left ventricle trabeculation without dysfunction. Expression studies of TAZ and LDB3 genes were conducted in family members and controls. In the proband, brother and father, LDB3 expression was similar to control cases. TAZ and LDB3 expression progressively declined with age in control both blood and myocardial samples. However, an endomyocardial biopsy performed in the proband at 6 months of age, showed significantly lower TAZ and LDB3 expression than in age-matched myocardial controls. We believe that the clinical, genetic and expression data support the hypothesis that tafazzins are essential during fetal and early post-natal life.
authors: Centre for Inherited Cardiovascular Diseases, Foundation IRCCS Policlinico San Matteo, Pavia, Italy.
authors: Nicola
authors: N
authors: Marziliano
authors: Savina
authors: S
authors: Mannarino
authors: Luisa
authors: L
authors: Nespoli
authors: Marta
authors: M
authors: Diegoli
authors: Michele
authors: M
authors: Pasotti
authors: Clara
authors: C
authors: Malattia
authors: Maurizia
authors: M
authors: Grasso
authors: Andrea
authors: A
authors: Pilotto
authors: Emanuele
authors: E
authors: Porcu
authors: Arturo
authors: A
authors: Raisaro
authors: Claudia
authors: C
authors: Raineri
authors: Roberto
authors: R
authors: Dore
authors: Pietro Paolo
authors: PP
authors: Maggio
authors: Agnese
authors: A
authors: Brega
authors: Eloisa
authors: E
authors: Arbustini
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D002311:Cardiomyopathy, Dilated / Q000151:congenital / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006352:Heart Ventricles / Q000002:abnormalities; D006579:Heterozygote; D006801:Humans; D060588:LIM Domain Proteins; D008297:Male; D008958:Models, Molecular; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C120696:LDB3 protein, human; D060588:LIM Domain Proteins; D011506:Proteins; D014157:Transcription Factors; D000217:Acyltransferases; C108675:TAFAZZIN protein, human