{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T00:33:36Z","timestamp":1760747616808,"version":"build-2065373602"},"reference-count":13,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1997,12]]},"abstract":"<jats:p>Holt-Oram syndrome is an autosomal dominant disorder characterised by radial ray and congenital heart defects. Recently, a gene for this disorder has been identified on chromosome 12q24.1, encoding a T box transcription factor. However, the functional role of the gene product is not completely understood. We present results of neurological, radiological, and muscle magnetic resonance imaging (MRI) investigations in 13 patients from eight unrelated families. Besides heart defects, clinical signs ranged from thenar abnormalities to bilateral phocomelia. The former were present in all patients. MRI showed hypoplasia of discrete muscles which clinically showed as non-progressive weakness. The structural pattern of residual muscles was normal on MRI, which together with normal muscular power, electromyography, and muscle enzyme investigations excluded a progressive neuromuscular disorder. The number and location of hypoplastic muscles correlated with the severity of skeletal involvement. Thus, patients with hypoplasia of large and proximal muscles had phocomelia, and those with mere intrinsic hand muscle hypoplasia had only a triphalangeal thumb or no skeletal malformation. On the basis of these observations, we conclude that disturbed fetal limb muscle development is involved in the bony malformations of the upper limbs.<\/jats:p>","DOI":"10.1136\/jmg.34.12.978","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"978-981","source":"Crossref","is-referenced-by-count":10,"title":["Muscular involvement in the Holt-Oram syndrome."],"prefix":"10.1136","volume":"34","author":[{"given":"S","family":"Spranger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Ulmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Tr\u00f6ger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Graf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H M","family":"Meinck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Spranger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1997,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1136\/jmg.33.4.300","article-title":"Holt-Oram syndrome: a clinical genetic study","volume":"33","author":"Newbury-Ecob, R.A.; Leanage, R.; Raeburn, J.A.; Young, I.D.","year":"1996","unstructured":"Newbury-Ecob RA, Leanage R, Raeburn JA, Young ID. Holt-Oram syndrome: a clinical genetic study. J Med Genet 1996;33:300-7.","journal-title":"J Med Genet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/ng0197-30","article-title":"Mutations in human (TBX5) cause limb and cardiac malformation in Holt-Oram syndrome","volume":"15","author":"Basson, C.T.; Bachinsky, D.R.; Lin, C.R.","year":"1997","unstructured":"Basson CT, Bachinsky DR, Lin CR, et al. Mutations in human (TBX5) cause limb and cardiac malformation in Holt-Oram syndrome. Nat Genet 1997;15:30-5.","journal-title":"Nat Genet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/ng0197-21","article-title":"Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family","volume":"15","author":"Li, Y.Q.; Newbury-Ecob, R.; Terrett, J.A.","year":"1997","unstructured":"Li YQ, Newbury-Ecob R, Terrett JA, et al. Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Nat Genet 1997;15:21-9.","journal-title":"Nat Genet"},{"key":"ref_4","first-page":"187","article-title":"Holt-Oram syndrome. Clinical and genetic study of a large family","volume":"18","author":"Gall, J.C.; Stern, A.M.; Cohen, M.M.; Adams, M.S.; Davidson, R.T.","year":"1966","unstructured":"Gall JC, Stern AM, Cohen MM, Adams MS, Davidson RT. Holt-Oram syndrome. Clinical and genetic study of a large family. Am J Hum Genet 1966; 18:187-200.","journal-title":"Am J Hum Genet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/S0022-3476(79)80758-1","article-title":"Holt-Oram syndrome","volume":"95","author":"Smith, A.T.; Sack, G.H.; Taylor, G.J.","year":"1979","unstructured":"Smith AT, Sack GH, Taylor GJ. Holt-Oram syndrome. Jf Pediatr 1979;95:538-43.","journal-title":"Jf Pediatr"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/ajmg.1320290415","article-title":"Variability of the Holt-Oram syndrome in Saudi individuals","volume":"29","author":"Najjar, H.; Mardini, M.; Tabbaa, R.; Nyhan, W.L.","year":"1988","unstructured":"Najjar H, Mardini M, Tabbaa R, Nyhan WL. Variability of the Holt-Oram syndrome in Saudi individuals. Am Jf Med Genet 1988;29:851-5.","journal-title":"Am Jf Med Genet"},{"key":"ref_7","first-page":"7780","article-title":"HoltOram syndrome mistaken for thalidomide embryopathy embryological considerations","volume":"138","author":"van Regemorter N; D, Haumont; C, Kirkpatrick","year":"1982","unstructured":"van Regemorter N, Haumont D, Kirkpatrick C, et al. HoltOram syndrome mistaken for thalidomide embryopathy embryological considerations. Eur J Pediatr 1982;138:7780.","journal-title":"Eur J Pediatr"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1136\/jmg.24.2.79","article-title":"Thrombocytopenia and absent radius (TAR) syndrome","volume":"24","author":"Hall, J.G.","year":"1987","unstructured":"Hall JG. Thrombocytopenia and absent radius (TAR) syndrome. JMed Genet 1987;24:79-83.","journal-title":"JMed Genet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1136\/jmg.19.6.412","article-title":"Spectrum of anomalies in Fanconi anaemia","volume":"19","author":"Glanz, A.; Fraser, F.C.","year":"1982","unstructured":"Glanz A, Fraser FC. Spectrum of anomalies in Fanconi anaemia.J Med Genet 1982;19:412-16.","journal-title":"J Med Genet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/S0022-3476(73)80024-1","article-title":"The VATER-association","volume":"82","author":"Quan, L.; Smith, D.W.","year":"1973","unstructured":"Quan L, Smith DW. The VATER-association. Jf Pediatr 1973;82: 104-7.","journal-title":"Jf Pediatr"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1399-0004.1991.tb03021.x","article-title":"Holt-Oram syndrome in four half-siblings with unaffected parents: brief clinical report","volume":"39","author":"Braulke, I.; Herzog, S.; Thies, U.; Zoll, B.","year":"1991","unstructured":"Braulke I, Herzog S, Thies U, Zoll B. Holt-Oram syndrome in four half-siblings with unaffected parents: brief clinical report. Clin Genet 1991;39:241-4.","journal-title":"Clin Genet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/0168-9525(90)90011-T","article-title":"The T genes in embryogenesis","volume":"10","author":"Herrmann, B.G.; Kispert, A.","year":"1994","unstructured":"Herrmann BG, Kispert A. The T genes in embryogenesis. Trends Genet 1994;10:280-6.","journal-title":"Trends Genet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0092-8674(05)80087-X","article-title":"Induction of muscle pioneers and floor plate is distinguished by the zebrafish no tail mutation","volume":"75","author":"Halpern, M.E.; Ho, K.R.; Walker, C.; Kimmel, C.B.","year":"1993","unstructured":"Halpern ME, Ho KR, Walker C, Kimmel CB. Induction of muscle pioneers and floor plate is distinguished by the zebrafish no tail mutation. 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