| #605355 | ||||||||||
| NEMALINE MYOPATHY 5; NEM5 | ||||||||||
| Alternative titles; symbols | ||||||||||
| NEMALINE MYOPATHY, AMISH TYPE; ANM AMISH NEMALINE MYOPATHY NEMALINE MYOPATHY, CAUSED BY MUTATION IN THE TROPONIN T1 GENE | ||||||||||
| Phenotype Gene Relationships | ||||||||||
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| Clinical Synopsis | ||||||||||
| TEXT | ||||||||||
| A number sign (#) is used with this entry because nemaline myopathy-5 (NEM5), also known as Amish nemaline myopathy, is caused by mutation in the gene encoding troponin T1 (TNNT1; 191041). For a discussion of genetic heterogeneity of nemaline myopathy, see NEM3 (161800). | ||||||||||
| Clinical Features | ||||||||||
| Between 1988 and 2000, Johnston et al. (2000) treated or obtained clinical information on 71 infants and young children from 33 nuclear families with an apparently unique form of nemaline myopathy. Since the disorder occurred among the Old Order Amish of Lancaster County, Pennsylvania, the authors referred to the autosomal recessive disorder as Amish nemaline myopathy (ANM). All neonates with ANM had tremors that were evident at birth or within a few days of birth and involved most skeletal muscle groups, especially the muscles of the jaw and lower limbs. These tremors subsided over the first 2 to 3 months of life. Mild proximal contractures present at birth gradually worsened with age, such that hip abduction was often limited to 10 degrees or less by age 12 months. Progressive muscle atrophy and weakness developed simultaneously with the contractures. Gross motor development was limited to rolling side to side, but forearm and hand function was normal, as was apparent intelligence. The characteristic severe pectus carinatum deformity, with rigidity of the chest wall, developed along with the proximal contractures. The authors suspected that tremors both in utero and for several weeks after birth might be a carrier manifestation: several sibs of affected individuals with normal outcomes had had abnormal trembling both in utero and for several weeks after birth. Neurologic examinations and, in one case, tests for hypoglycemia and hypocalcemia, were normal in these sibs. Johnston et al. (2000) estimated that the disorder has an incidence of 1 in 500 among the Amish. | ||||||||||
| Molecular Genetics | ||||||||||
| Using a genealogy database, automated pedigree software, and linkage analysis of DNA samples from 4 sibships, Johnston et al. (2000) identified an interval of approximately 2 cM on 19q13.4 that was homozygous in all affected individuals. Since the gene for the sarcomeric thin-filament protein, slow skeletal muscle troponin T, maps to this interval, Johnston et al. (2000) sequenced the gene and identified a nonsense mutation predicted to truncate the protein at amino acid 179 (191041.0001). | ||||||||||
| REFERENCES | ||||||||||
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