How to cite this article: McPherson E, Turner L, Zador I, Reynolds K, Macgregor D, Giampietro PF. 2009. Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation. Am J Med Genet Part A 149A:567–572.
Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation†
Article first published online: 12 MAR 2009
Copyright © 2009 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 149A, Issue 4, pages 567–572, April 2009
How to Cite
McPherson, E., Turner, L., Zador, I., Reynolds, K., Macgregor, D. and Giampietro, P. F. (2009), Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation. Am. J. Med. Genet., 149A: 567–572. doi: 10.1002/ajmg.a.32627
- Issue published online: 24 MAR 2009
- Article first published online: 12 MAR 2009
- Manuscript Accepted: 8 OCT 2008
- Manuscript Received: 29 JAN 2008
- lamin A;
- malouf syndrome;
- premature ovarian failure;
- progeroid syndrome
Two unrelated young women presented with similar dysmorphic features including severe retrognathia, beaked nose, narrow chest, sloping shoulders, and an acrogeric appearance of the hands and feet. Neither had any evidence of skeletal myopathy, but both developed progressive dilated cardiomyopathy, both experienced premature ovarian failure, and both were found to have the same heterozygous novel missense mutation c.176T>G in exon 1 of the LMNA gene, resulting in a leucine to arginine change at codon 59 (Leu59Arg). Mutations in the LMNA gene cause a variety of disorders including dilated cardiomyopathy, muscular dystrophy, familial lipodystrophy, progeria, atypical progeroid syndromes, and mandibuloacral dysplasia. Genotype–phenotype correlation has been reported for some of these conditions. Our patients are the only ones known to have the specific mutation Leu59Arg and also share a set of features not entirely consistent with any of the laminopathies previously described. A previously reported patient with an adjacent mutation (Ala57Pro) had “atypical Werner syndrome” with dilated cardiomyopathy, hypogonadism, and sloping shoulders. While each of these clinical features does occur in other laminopathy syndromes, these patients form a phenotypic cluster distinct from other laminopathies and clinically overlapping with Malouf syndrome. LMNA sequencing should be considered for patients presenting with dilated cardiomyopathy and hypergonadotropic hypogonadism, including those previously diagnosed with Malouf syndrome. © 2009 Wiley-Liss, Inc.