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A novel nemaline myopathy in the Amish caused by a mutation in troponin T1.
Am J Hum Genet. 2000 Oct; 67(4):814-21.AJ

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 approximately 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 approximately 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.

Authors+Show Affiliations

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA. jjohnsto@nhgri.nih.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10952871

Citation

Johnston, J J., et al. "A Novel Nemaline Myopathy in the Amish Caused By a Mutation in Troponin T1." American Journal of Human Genetics, vol. 67, no. 4, 2000, pp. 814-21.
Johnston JJ, Kelley RI, Crawford TO, et al. A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. Am J Hum Genet. 2000;67(4):814-21.
Johnston, J. J., Kelley, R. I., Crawford, T. O., Morton, D. H., Agarwala, R., Koch, T., Schäffer, A. A., Francomano, C. A., & 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), 814-21.
Johnston JJ, et al. A Novel Nemaline Myopathy in the Amish Caused By a Mutation in Troponin T1. Am J Hum Genet. 2000;67(4):814-21. PubMed PMID: 10952871.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. AU - Johnston,J J, AU - Kelley,R I, AU - Crawford,T O, AU - Morton,D H, AU - Agarwala,R, AU - Koch,T, AU - Schäffer,A A, AU - Francomano,C A, AU - Biesecker,L G, Y1 - 2000/08/21/ PY - 2000/06/05/received PY - 2000/08/02/accepted PY - 2000/8/23/pubmed PY - 2001/2/28/medline PY - 2000/8/23/entrez SP - 814 EP - 21 JF - American journal of human genetics JO - Am. J. Hum. Genet. VL - 67 IS - 4 N2 - 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 approximately 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 approximately 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. SN - 0002-9297 UR - https://www.unboundmedicine.com/medline/citation/10952871/A_novel_nemaline_myopathy_in_the_Amish_caused_by_a_mutation_in_troponin_T1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9297(07)63275-3 DB - PRIME DP - Unbound Medicine ER -