A novel nemaline myopathy in the Amish caused by a mutation in troponin T1

J. J. Johnston, R. I. Kelley, Thomas Owen Crawford, D. H. Morton, R. Agarwala, T. Koch, A. A. Schaffer, Clair Ann Francomano, L. G. Biesecker

Research output: Contribution to journalArticle

Abstract

The nemaline myopathies are characterized by weakness and eosinophilic, rodlike (nemaline) inclusions in muscle fibers. Amish nemaline myopathy is a form of nemaline myopathy common among the Old Order Amish. In the first months of life, affected infants have tremors with hypotonia and mild contractures of the shoulders and hips. Progressive worsening of the proximal contractures, weakness, and a pectus carinatum deformity develop before the children die of respiratory insufficiency, usually in the second year. The disorder has an incidence of ~1 in 500 among the Amish, and it is inherited in an autosomal recessive pattern. Using a genealogy database, automated pedigree software, and linkage analysis of DNA samples from four sibships, we identified an ~2-cM interval on chromosome 19q13.4 that was homozygous in all affected individuals. The gene for the sarcomeric thin-filament protein, slow skeletal muscle troponin T (TNNT1), maps to this interval and was sequenced. We identified a stop codon in exon 11, predicted to truncate the protein at amino acid 179, which segregates with the disease. We conclude that Amish nemaline myopathy is a distinct, heritable, myopathic disorder caused by a mutation in TNNT1.

Original languageEnglish (US)
Pages (from-to)814-821
Number of pages8
JournalAmerican Journal of Human Genetics
Volume67
Issue number4
DOIs
StatePublished - 2000

Fingerprint

Amish
Nemaline Myopathies
Troponin T
Hip Contracture
Genealogy and Heraldry
Mutation
Muscle Hypotonia
Terminator Codon
Contracture
Tremor
Pedigree
Respiratory Insufficiency
Exons
Skeletal Muscle
Proteins
Software
Chromosomes
Databases
Amino Acids
Muscles

ASJC Scopus subject areas

  • Genetics

Cite this

Johnston, J. J., Kelley, R. I., Crawford, T. O., Morton, D. H., Agarwala, R., Koch, T., ... Biesecker, L. G. (2000). A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. American Journal of Human Genetics, 67(4), 814-821. https://doi.org/10.1086/303089

A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. / Johnston, J. J.; Kelley, R. I.; Crawford, Thomas Owen; Morton, D. H.; Agarwala, R.; Koch, T.; Schaffer, A. A.; Francomano, Clair Ann; Biesecker, L. G.

In: American Journal of Human Genetics, Vol. 67, No. 4, 2000, p. 814-821.

Research output: Contribution to journalArticle

Johnston, JJ, Kelley, RI, Crawford, TO, Morton, DH, Agarwala, R, Koch, T, Schaffer, AA, Francomano, CA & Biesecker, LG 2000, 'A novel nemaline myopathy in the Amish caused by a mutation in troponin T1', American Journal of Human Genetics, vol. 67, no. 4, pp. 814-821. https://doi.org/10.1086/303089
Johnston, J. J. ; Kelley, R. I. ; Crawford, Thomas Owen ; Morton, D. H. ; Agarwala, R. ; Koch, T. ; Schaffer, A. A. ; Francomano, Clair Ann ; Biesecker, L. G. / A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. In: American Journal of Human Genetics. 2000 ; Vol. 67, No. 4. pp. 814-821.
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