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(Circulation. 2000;101:473.)
© 2000 American Heart Association, Inc.

Brief Rapid Communications

Lamin A/C Gene Mutation Associated With Dilated Cardiomyopathy With Variable Skeletal Muscle Involvement

Gary L. Brodsky, PhD; Francesco Muntoni, MD; Snjezana Miocic, MD; Gianfranco Sinagra, MD; Caroline Sewry, PhD; Luisa Mestroni, MD

From the University of Colorado Cardiovascular Institute, Denver (G.L.B., L.M.); the Department of Paediatrics, Hammersmith Hospital, Imperial College School of Medicine, London, UK (F.M., C.S.); and ICGEB and Division of Cardiology, Ospedale Maggiore, Trieste, Italy (S.M., G.S.).

Correspondence to Luisa Mestroni, CU-CVI, UCHSC at Fitzsimons, Bldg 500, Room 2115, PO Box 6508, Mail Stop F-442, Aurora, CO 80045-0508. E-mail luisa.mestroni{at}uchsc.edu

	Abstract

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Background—Dilated cardiomyopathy is a form of heart muscle disease characterized by impaired systolic function and ventricular dilation. Familial transmission of the disease is frequently observed, and genetic heterogeneity is indicated by clinical and morphological variability in the disease phenotype. In the family MDDC1 reported here, the disease phenotype is severe and characterized by an autosomal dominant pattern of transmission. In addition, the majority of affected family members show signs of mild skeletal muscle involvement.

Methods and Results—On the basis of the clinical observation of both cardiac and skeletal muscle abnormalities in the MDDC1 family, the lamin A/C gene was examined in this kindred. Coding regions were polymerase chain reaction–amplified from genomic DNA and sequenced. A single nucleotide deletion was identified within exon 6, and all affected individuals were found to be heterozygous for this deletion.

Conclusions—Heterozygosity for a single nucleotide deletion in exon 6 of lamin A/C segregates with both the cardiac and skeletal abnormalities observed in the MDDC1 family.

Key Words: cardiomyopathy • genetics • molecular biology • muscles

	Introduction

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Dilated cardiomyopathy (DCM) is a form of heart muscle disease characterized by impaired systolic function and ventricular dilation of the left, or both, ventricles.¹ Clinical and molecular genetic studies have resulted in the identification of 11 candidate disease loci for inherited DCM. However, only 4 disease genes responsible for DCM have been identified. These include cardiac actin,² dystrophin,^{3 4} tafazzin,⁵ and desmin.⁶

The family MDDC1 has a severe DCM phenotype that is inherited in an autosomal dominant pattern.⁷ The majority of affected family members demonstrate a mild form of skeletal muscle involvement.⁷ Cardiac abnormalities have been reported in Duchenne, Becker, and limb-girdle (LGMD) muscular dystrophy.^{8 9} In autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2), skeletal muscle weakness and wasting is often associated with conduction defects and myocardial dysfunction.¹⁰

Recently, mutations in the lamin A/C gene have been identified in 5 EDMD2 families.¹¹ The phenotypic similarities shared by EDMD2 patients and affected individuals in the MDDC1 pedigree led to the consideration of the lamin A/C gene as a candidate for the disease phenotype observed in this family. To test this hypothesis, we analyzed the lamin A/C gene for mutations and examined the segregation of lamin A/C mutations in the MDDC1 pedigree.

	Methods

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Subjects
After informed consent and approval by the institutional review committee, 14 members of the MDDC1 family were examined as previously described.⁷ Patients were evaluated by history, physical examination, ECG, and echocardiography (M-mode, 2D, and Doppler). Subjects II-1 and II-5 underwent cardiac catheterization, including ventriculography, coronary angiography, and endomyocardial biopsy. Neuromuscular investigations included electromyography and skeletal muscle biopsy. DCM status was classified as affected, unaffected, or unknown according to previously published criteria.¹¹

Lamin A/C Mutation Analysis
The coding regions of the lamin A/C gene from patient II-1 were sequenced as previously described.¹¹ Exon 6 was amplified from genomic DNA isolated from MDDC1 family members with primers flanking the exon (5'-ATCCTGGAGAGAGTAGCCAG-3' and 5'-TCTAGTCAAGGCCAGTTGCC-3'). The resulting PCR amplimers were sequenced in both directions. Single-strand conformation polymorphism (SSCP)/heteroduplex (HDX) analysis¹² was performed on the MDDC1 amplimers and amplimers from 50 ethnically matched control subjects (100 chromosomes).

	Results

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Fourteen members of the MDDC1 family were examined (Figure 1A), and 5 of these individuals were classified as affected. The main clinical features observed are summarized in the Table. Patient II-5 displayed a pure DCM phenotype, whereas patients II-1, III-3, and III-4 had mild skeletal muscle involvement with slight calf hypertrophy and mild proximal limb girdle muscle weakness. Patient III-4 displayed mild atrophy of the biceps brachii and peroneal muscles and the supraspinatus and infraspinatus muscles, as well as spinal rigidity. Endomyocardial biopsies were performed on II-1 and II-5 and showed significant abnormalities compatible with acute myocarditis in the proband (II-5) and healing myocarditis in his brother (II-1)⁷ (Figure 2A). Muscle pathology indicated mild dystrophic changes in patients II-1, III-3, and III-4 (Figure 2B). Therefore, patient II-5 was classified as having pure DCM, whereas patients II-1 and III-3 displayed symptoms of LGMD and patient III-4 displayed symptoms characteristic of EDMD (Table). Serum creatine kinase levels were above normal limits in 3 of the 5 affected family members (Table).

View larger version (54K): [in this window] [in a new window]   Figure 1. Heterozygous lamin A/C mutations in MDDC1 patients. A, Pedigree of MDDC1 family with individuals indicated by generation and pedigree number. Solid squares (males) and circles (females) indicate affected status, open symbols indicate unaffected status, and shaded symbols indicate unknown disease status (patient II-10 has isolated left ventricular conduction delay). B, SSCP/HDX analysis showing homoduplex (a), heteroduplex (b), and SSCP (c) bands. Heteroduplex band cosegregates with disease within family. C, DNA sequencing fluorograms demonstrating heterozygosity for lamin A/C nt 959 deletion. Forward sequencing reaction of exon 6 from an unaffected MDDC1 family member (a) yields a single DNA sequence. Same sequencing reaction performed on an affected MDDC1 family member (b) yields a single DNA sequence through nt 959. Heterozygosity for T959 deletion is indicated by presence of overlapping wild-type lamin A/C sequence and a lamin A/C sequence shifted 1 nt to left (5' end) beyond nt 959. Below fluorograms are predicted wild-type (a) and mutant (b) protein sequences, starting at codon 317. Novel mutant peptide sequences caused by frame shift are shown in blue along with resulting premature termination (Stop) codon. Nuclear localization signal, which is absent in mutant protein, is shown in red.

View this table: [in this window] [in a new window]   Table 1. Clinical Features of MDDC1 Family Members Heterozygous for the Lamin A/C Deletion Mutation

View larger version (132K): [in this window] [in a new window]   Figure 2. Abnormalities of cardiac and skeletal muscle in MDDC1 patients. A, Endomyocardial biopsy (hematoxylin-eosin stain, magnification x40, bar=0.1 mm) of individual II-1 at disease onset (ejection fraction, 53%) showing interstitial edema, hypertrophy, fibrosis, and cellular infiltrates, suggestive of healing myocarditis. B, Skeletal muscle biopsy showing variability of fiber size, with both atrophic and hypertrophic fibers, several splittings, an increase in internal nuclei, focal signs of degeneration and regeneration with basophilic fibers, and a mild increase in endomysial connective tissue (hematoxylin-eosin stain, magnification x25, bar=25 µm).

DNA sequence analysis of the complete lamin A/C coding region from patient II-1 revealed heterozygosity for a single nucleotide deletion at position 959, which is within exon 6 (Figure 1C). Sequence analysis of exon 6 in all available family members demonstrated that all affected individuals are heterozygous for the exon 6 deletion, whereas all unaffected family members are homozygous for the normal lamin A/C allele. SSCP/HDX analysis demonstrated the presence of a heteroduplex band formed by the wild-type and deletion alleles (Figure 1B). SSCP/HDX analysis was then used to demonstrate that the nt 959 deletion was not present in 100 control chromosomes from unaffected individuals (data not shown).

	Discussion

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The present study identifies a lamin A/C gene mutation that segregates with the disease phenotype in a family with severe DCM and variable skeletal muscle involvement. The single nucleotide deletion identified in MDDC1 results in pure DCM with conduction defects, DCM with EDMD-like skeletal muscle abnormalities, and DCM with LGMD-like skeletal muscle dystrophy. These findings demonstrate that a lamin A/C gene mutation can result in a pure DCM phenotype without skeletal muscle involvement and that LGMD1-B, which maps to the same genetic locus,⁹ is likely to be due to mutations in the lamin A/C gene. Finally, the identification of this mutation in the lamin A/C gene further supports the model that DCM is caused by mutations in cytoskeletal proteins.

The lamin A/C gene encodes 2 proteins that are members of the intermediate filament class of cytoskeletal proteins. The nt 959 deletion is predicted to result in a mutant protein that shares its 318-amino-acid N-terminal sequence with that of lamins A and C. The frame shift causes the addition of 158 novel amino acids to the C-terminal end of the mutant protein. The mutation is predicted to leave part of the rod domain, which is involved in dimerization, intact while removing the C-terminal globular domain, lamin A processing domain, and nuclear localization signal. The unique C-terminal end of the mutant protein shows no homology to previously identified protein sequences.

The variable phenotype of skeletal muscle involvement in MDDC1 suggests that the mutation responsible for this disease differs in mechanism from the mutations resulting in AD-EDMD.¹¹ However, it remains to be determined whether haploinsufficiency, due to mutant mRNA or protein instability, or a poison peptide effect is responsible for DCM in this family. Although lamin A localization was found to be normal in cardiac myocytes isolated from EDMD2 patients carrying a nonsense mutation in codon 6,¹¹ the abundance of the protein was not assayed and expression of the mutant protein was not specifically examined.

In conclusion, the results described here demonstrate that a single mutation in the lamin A/C gene can result in a phenotype of DCM with a history of conduction defects, or DCM with EDMD-like symptoms, or DCM with LGMD-like symptoms. These results further support the hypotheses that DCM arises from mutations in cytoskeletal proteins and that LGMD1-B is also due to mutations in the lamin A/C gene. Although the identification of this mutation enhances the possibilities for early diagnosis and prevention of DCM, characterization of the mechanism by which this mutation causes the MDDC1 phenotype is likely to provide significant insights into the molecular basis of both DCM and muscular dystrophy.

	Acknowledgments

 
Telethon grant E.1029 and the Heart Muscle Disease Study Group (Trieste, Italy) are gratefully acknowledged. We thank the family members for their participation in these studies.

Received October 11, 1999; revision received November 15, 1999; accepted December 6, 1999.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O’Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I, Martin I, Nordet P. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies. Circulation. 1996;93:841–842.[Free Full Text]

2. Olson TM, Michels VV, Thibodeau SN, Tai Y, Keating MT. Actin mutation in dilated cardiomyopathy, a heritable form of heart failure. Science. 1998;280:750–752.[Abstract/Free Full Text]

3. Muntoni F, Cau M, Ganau A, Congiu R, Arvedi G, Mateddu A, Morrosu MG, Cianchetti C, Realdi G, Cao A, Melis MA. Deletion of the dystrophin muscle-promoter region associated with X-linked dilated cardiomyopathy. N Engl J Med. 1993;329:921–925.[Free Full Text]

4. Towbin JA, Hejtmancik F, Brink P, Gelb BD, Zhu XM, Chamberlain JS, McCabe ERB, Swift M. X-linked cardiomyopathy (XLCM): molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus. Circulation. 1993;87:1854–1865.[Abstract/Free Full Text]

5. D’Adamo P, Fassone L, Gedeon A, Janssen EAM, Bione S, Bolhuis PA, Barth PG, Wilson M, Haan E, Orstavik KH, Patton MA, Green AJ, Zammarchi E, Donati MA, Toniolo D. The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies. Am J Hum Genet. 1997;61:862–867.[Medline] [Order article via Infotrieve]

6. Li D, Tapscoft T, Gonzalez O, Burch PE, Quinones MA, Zoghbi WA, Hill R, Bachinski LL, Mann DL, Roberts R. Desmin mutation responsible for idiopathic dilated cardiomyopathy. Circulation. 1999;100:461–464.[Abstract/Free Full Text]

7. Mestroni L, Rocco C, Gregori D, Sinagra G, Di Lenarda A, Miocic S, Vatta M, Pinamonti B, Muntoni F, Caforio A, McKenna WJ, Falaschi A, Giacca M, Camerini F. Familial dilated cardiomyopathy: evidence for genetic and phenotypic heterogeneity. J Am Coll Cardiol. 1999;34:181–190.[Abstract/Free Full Text]

8. Cox GF, Kunkel LM. Dystrophies and heart disease. Curr Opin Cardiol. 1997;12:329–343.[Medline] [Order article via Infotrieve]

9. van der Kooi AJ, van Meegen M, Ledderhof TM, McNally EM, de Visser M, Bolhuis PA. Genetic localization of a newly recognized autosomal dominant limb-girdle muscular dystrophy with cardiac involvement (LGMD1B) to chromosome 1q11–21. Am J Hum Genet. 1997;60:891–895.[Medline] [Order article via Infotrieve]

10. Emery AE. Emery-Dreifuss syndrome. J Med Genet.. 1989;26:637–641.[Abstract/Free Full Text]

11. Bonne G, Di Barletta MR, Varnous S, Bécane H, Hammouda E, Merlini L, Muntoni F, Greenberg CR, Gary F, Urtizberea J, Duboc D, Fardeau M, Toniolo D, Schwartz K. Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy. Nat Genet. 1999;21:285–288.[Medline] [Order article via Infotrieve]

12. Lee ST, Park SK, Lee H, Lee JS, Park YW. DNA-based prenatal diagnosis of a Korean family with tyrosinase-related oculocutaneous albinism (OCA1). Jpn J Hum Genet. 1997;42:499–505.[Medline] [Order article via Infotrieve]

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				Y. Miyamoto, H. Akita, N. Shiga, E. Takai, C. Iwai, K. Mizutani, H. Kawai, A. Takarada, and M. Yokoyama Frequency and clinical characteristics of dilated cardiomyopathy caused by desmin gene mutation in a Japanese population Eur. Heart J., December 2, 2001; 22(24): 2284 - 2289. [Abstract] [PDF]

				H. H.-J. Schmidt, H. Lochs, G. L. Brodsky, L. Mestroni, F. Muntoni, C. Sewry, S. Miocic, and G. Sinagra Lamin A/C Gene Mutation Associated With Dilated Cardiomyopathy With Variable Skeletal Muscle Involvement Response Circulation, January 30, 2001; 103 (4): e20 - e20. [Full Text] [PDF]

				C. Hutchison, M Alvarez-Reyes, and O. Vaughan Lamins in disease: why do ubiquitously expressed nuclear envelope proteins give rise to tissue-specific disease phenotypes? J. Cell Sci., January 1, 2001; 114(1): 9 - 19. [Abstract] [PDF]

				M KOMAJDA Genetics of dilated cardiomyopathy: a molecular maze? Heart, November 1, 2000; 84(5): 463 - 464. [Full Text]

				A. Muchir, G. Bonne, A. J. van der Kooi, M. van Meegen, F. Baas, P. A. Bolhuis, M. de Visser, and K. Schwartz Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B) Hum. Mol. Genet., May 22, 2000; 9(9): 1453 - 1459. [Abstract] [Full Text] [PDF]

				J. Stypmann, K. Glaser, W. Roth, D. J. Tobin, I. Petermann, R. Matthias, G. Monnig, W. Haverkamp, G. Breithardt, W. Schmahl, et al. Dilated cardiomyopathy in mice deficient for the lysosomal cysteine peptidase cathepsin L PNAS, April 30, 2002; 99(9): 6234 - 6239. [Abstract] [Full Text] [PDF]

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