BACKGROUND: The tafazzin gene (TAZ) is located at Xq28 and encodes a protein involved in the transacylation of cardiolipin, an essential mitochondrial phospholipid. Mutations in TAZ are associated with Barth syndrome (BTHS), the X-linked recessive condition with dilated cardiomyopathy, skeletal myopathy, growth retardation, neutropenia and organic aciduria. TAZ mutations also contribute to left ventricular noncompaction (LVNC), a cardiomyopathy characterized by loose, trabeculated myocardium. CASE REPORT: We report a family with a novel TAZ mutation and the clinical spectrum from severe BTHS in an infant to skeletal myopathy with LVNC in an adult, the oldest individual with BTHS reported. The proband is a 51-year-old male with muscle weakness since early childhood. He remained stable until the age of 43. His initial evaluations found LVNC and borderline neutropenia with no elevation of urine 3-methylglutaconic acid. The proband's great nephew is a 3-year-old who presented at birth with poor feeding, hypotonia, lactic acidosis and hypoglycemia. At three months he was admitted with failure to thrive, lethargy and respiratory distress due to heart failure. Cardiac studies revealed dilated cardiomyopathy with a spongiform trabeculated pattern of the left ventricle. Laboratory studies showed cyclic neutropenia and elevated urine 3-methylglutaconic and 3-methylglutaric acids. At age 11months the patient had a heart transplant. We conducted sequence analysis of the TAZ gene for two affected individuals, the proband first and then his great-nephew. A novel, hemizygous nonsense mutation in TAZ exon 7 (c.583G>T, p.Gly195X) was detected. CONCLUSION: At his current age of 51years-old, the proband is the oldest surviving individual reported with a confirmed molecular diagnosis and features of Barth syndrome. Further studies will be conducted to identify the genetic modifying factor(s) associated with the wide phenotypic range seen in this family.
BACKGROUND: The tafazzin gene (TAZ) is located at Xq28 and encodes a protein involved in the transacylation of cardiolipin, an essential mitochondrial phospholipid. Mutations in TAZ are associated with Barth syndrome (BTHS), the X-linked recessive condition with dilated cardiomyopathy, skeletal myopathy, growth retardation, neutropenia and organic aciduria. TAZ mutations also contribute to left ventricular noncompaction (LVNC), a cardiomyopathy characterized by loose, trabeculated myocardium. CASE REPORT: We report a family with a novel TAZ mutation and the clinical spectrum from severe BTHS in an infant to skeletal myopathy with LVNC in an adult, the oldest individual with BTHS reported. The proband is a 51-year-old male with muscle weakness since early childhood. He remained stable until the age of 43. His initial evaluations found LVNC and borderline neutropenia with no elevation of urine 3-methylglutaconic acid. The proband's great nephew is a 3-year-old who presented at birth with poor feeding, hypotonia, lactic acidosis and hypoglycemia. At three months he was admitted with failure to thrive, lethargy and respiratory distress due to heart failure. Cardiac studies revealed dilated cardiomyopathy with a spongiform trabeculated pattern of the left ventricle. Laboratory studies showed cyclic neutropenia and elevated urine 3-methylglutaconic and 3-methylglutaric acids. At age 11months the patient had a heart transplant. We conducted sequence analysis of the TAZ gene for two affected individuals, the proband first and then his great-nephew. A novel, hemizygous nonsense mutation in TAZ exon 7 (c.583G>T, p.Gly195X) was detected. CONCLUSION: At his current age of 51years-old, the proband is the oldest surviving individual reported with a confirmed molecular diagnosis and features of Barth syndrome. Further studies will be conducted to identify the genetic modifying factor(s) associated with the wide phenotypic range seen in this family.
Authors: J Johnston; R I Kelley; A Feigenbaum; G F Cox; G S Iyer; V L Funanage; R Proujansky Journal: Am J Hum Genet Date: 1997-11 Impact factor: 11.025
Authors: F Ichida; Y Hamamichi; T Miyawaki; Y Ono; T Kamiya; T Akagi; H Hamada; O Hirose; T Isobe; K Yamada; S Kurotobi; H Mito; T Miyake; Y Murakami; T Nishi; M Shinohara; M Seguchi; S Tashiro; H Tomimatsu Journal: J Am Coll Cardiol Date: 1999-07 Impact factor: 24.094
Authors: Carolyn T Spencer; Randall M Bryant; Jane Day; Iris L Gonzalez; Steven D Colan; W Reid Thompson; Julie Berthy; Sharon P Redfearn; Barry J Byrne Journal: Pediatrics Date: 2006-07-17 Impact factor: 7.124
Authors: C T Spencer; B J Byrne; M H Gewitz; S B Wechsler; A C Kao; E P Gerstenfeld; A D Merliss; M P Carboni; R M Bryant Journal: Pediatr Cardiol Date: 2005 Sep-Oct Impact factor: 1.655
Authors: Peter G Barth; Fredoen Valianpour; Valerie M Bowen; Jan Lam; Marinus Duran; Frédéric M Vaz; Ronald J A Wanders Journal: Am J Med Genet A Date: 2004-05-01 Impact factor: 2.802
Authors: Jordan M Johnson; Patrick J Ferrara; Anthony R P Verkerke; Chanel B Coleman; Edward J Wentzler; P Darrell Neufer; Kimberly A Kew; Lisandra E de Castro Brás; Katsuhiko Funai Journal: J Mol Cell Cardiol Date: 2018-07-02 Impact factor: 5.000
Authors: Sarah L N Clarke; Ann Bowron; Iris L Gonzalez; Sarah J Groves; Ruth Newbury-Ecob; Nicol Clayton; Robin P Martin; Beverly Tsai-Goodman; Vanessa Garratt; Michael Ashworth; Valerie M Bowen; Katherine R McCurdy; Michaela K Damin; Carolyn T Spencer; Matthew J Toth; Richard I Kelley; Colin G Steward Journal: Orphanet J Rare Dis Date: 2013-02-12 Impact factor: 4.123