Abstract
Loss-of-function mutations in the G4.5 gene have been shown to cause Barth syndrome (BTHS), an X-linked disorder characterized by cardiac and skeletal myopathy, short stature, and neutropenia. We recently reported a family with a severe X-linked cardiomyopathy described as isolated noncompaction of the left ventricular myocardium (INVM). Other findings associated with BTHS (skeletal myopathy, neutropenia, growth retardation, elevated urinary organic acids, and mitochondrial abnormalities) were either absent or inconsistent. A linkage study of the X chromosome localized INVM to the Xq28 region near the BTHS locus, suggesting that these disorders are allelic. We screened the G4.5 gene for mutations in this family with SSCP and direct sequencing and found a novel glycine-to-arginine substitution at position 197. This position is conserved in a homologous Caenorhabditis elegans protein. We conclude that INVM is a severe allelic variant of BTHS with a specific effect on the heart. This finding provides further structure-function information about the G4.5 gene product and has implications for unexplained cases of severe infantile hypertrophic cardiomyopathy in males.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
- Barth P. G., Scholte H. R., Berden J. A., Van der Klei-Van Moorsel J. M., Luyt-Houwen I. E., Van 't Veer-Korthof E. T., Van der Harten J. J., Sobotka-Plojhar M. A. An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes. J Neurol Sci. 1983 Dec;62(1-3):327–355. doi: 10.1016/0022-510x(83)90209-5. [DOI] [PubMed] [Google Scholar]
- Bione S., D'Adamo P., Maestrini E., Gedeon A. K., Bolhuis P. A., Toniolo D. A novel X-linked gene, G4.5. is responsible for Barth syndrome. Nat Genet. 1996 Apr;12(4):385–389. doi: 10.1038/ng0496-385. [DOI] [PubMed] [Google Scholar]
- Bleyl S. B., Mumford B. R., Brown-Harrison M. C., Pagotto L. T., Carey J. C., Pysher T. J., Ward K., Chin T. K. Xq28-linked noncompaction of the left ventricular myocardium: prenatal diagnosis and pathologic analysis of affected individuals. Am J Med Genet. 1997 Oct 31;72(3):257–265. [PubMed] [Google Scholar]
- Bleyl S., Nelson L., Odelberg S. J., Ruttenberg H. D., Otterud B., Leppert M., Ward K. A gene for familial total anomalous pulmonary venous return maps to chromosome 4p13-q12. Am J Hum Genet. 1995 Feb;56(2):408–415. [PMC free article] [PubMed] [Google Scholar]
- Chin T. K., Perloff J. K., Williams R. G., Jue K., Mohrmann R. Isolated noncompaction of left ventricular myocardium. A study of eight cases. Circulation. 1990 Aug;82(2):507–513. doi: 10.1161/01.cir.82.2.507. [DOI] [PubMed] [Google Scholar]
- Gedeon A. K., Wilson M. J., Colley A. C., Sillence D. O., Mulley J. C. X linked fatal infantile cardiomyopathy maps to Xq28 and is possibly allelic to Barth syndrome. J Med Genet. 1995 May;32(5):383–388. doi: 10.1136/jmg.32.5.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lathrop G. M., Lalouel J. M., Julier C., Ott J. Multilocus linkage analysis in humans: detection of linkage and estimation of recombination. Am J Hum Genet. 1985 May;37(3):482–498. [PMC free article] [PubMed] [Google Scholar]
- Palmieri G., Romano G., Ciccodicola A., Casamassimi A., Campanile C., Esposito T., Cappa V., Lania A., Johnson S., Reinbold R. YAC contig organization and CpG island analysis in Xq28. Genomics. 1994 Nov 1;24(1):149–158. doi: 10.1006/geno.1994.1592. [DOI] [PubMed] [Google Scholar]
- Pearson W. R. Rapid and sensitive sequence comparison with FASTP and FASTA. Methods Enzymol. 1990;183:63–98. doi: 10.1016/0076-6879(90)83007-v. [DOI] [PubMed] [Google Scholar]
- Rust S., Funke H., Assmann G. Mutagenically separated PCR (MS-PCR): a highly specific one step procedure for easy mutation detection. Nucleic Acids Res. 1993 Aug 11;21(16):3623–3629. doi: 10.1093/nar/21.16.3623. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilson R., Ainscough R., Anderson K., Baynes C., Berks M., Bonfield J., Burton J., Connell M., Copsey T., Cooper J. 2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans. Nature. 1994 Mar 3;368(6466):32–38. doi: 10.1038/368032a0. [DOI] [PubMed] [Google Scholar]