Barth syndrome associated with compound hemizygosity and heterozygosity of the TAZ and LDB3 Genes

Nicola Marziliano, Savina Mannarino, Luisa Nespoli, Marta Diegoli, Michele Pasotti, Clara Malattia, Maurizia Grasso, Andrea Pilotto, Emanuele Porcu, Arturo Raisaro, Claudia Raineri, Roberto Dore, Pietro Paolo Maggio, Agnese Brega, Eloisa Arbustini

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)907-915
Number of pages9
JournalAmerican Journal of Medical Genetics, Part A
Volume143
Issue number9
DOIs
Publication statusPublished - May 1 2007

Fingerprint

Barth Syndrome
Dilated Cardiomyopathy
Nuclear Family
Oral Ulcer
Genes
Mothers
Muscular Diseases
Fathers
Siblings
Aphthous Stomatitis
Mutation
Spontaneous Abortion
Neutropenia
Left Ventricular Function
Heart Ventricles
Cardiac Arrhythmias
Mitochondria
Magnetic Resonance Imaging
Biopsy

Keywords

  • Barth syndrome
  • Dilated cardiomyopathy (DCM)
  • Expression profiles
  • Left ventricle non-compaction (LVNC)
  • LIM domain-binding 3 protein (LDB3)
  • Tafazzin (TAZ)

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Barth syndrome associated with compound hemizygosity and heterozygosity of the TAZ and LDB3 Genes. / Marziliano, Nicola; Mannarino, Savina; Nespoli, Luisa; Diegoli, Marta; Pasotti, Michele; Malattia, Clara; Grasso, Maurizia; Pilotto, Andrea; Porcu, Emanuele; Raisaro, Arturo; Raineri, Claudia; Dore, Roberto; Maggio, Pietro Paolo; Brega, Agnese; Arbustini, Eloisa.

In: American Journal of Medical Genetics, Part A, Vol. 143, No. 9, 01.05.2007, p. 907-915.

Research output: Contribution to journalArticle

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AU - Mannarino, Savina

AU - Nespoli, Luisa

AU - Diegoli, Marta

AU - Pasotti, Michele

AU - Malattia, Clara

AU - Grasso, Maurizia

AU - Pilotto, Andrea

AU - Porcu, Emanuele

AU - Raisaro, Arturo

AU - Raineri, Claudia

AU - Dore, Roberto

AU - Maggio, Pietro Paolo

AU - Brega, Agnese

AU - Arbustini, Eloisa

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