Nature Genetics 15,[131][132][133][134][135][136].Editorial changes after the authors correction of the proofs resulted in the incorrect substitution of the word 'eutherian' for the word 'therian' throughout the text. We would like to clarify that the lnfraclass Eutheria refers to the 'placental' mammals only, whereas the Subclass Theria includes both the Infraclass Metatheria (marsupials) and the Infraclass Eutheria. Substitutions of'therian' for 'eutherian' should be made on: page 131, Abstract, line 7; page 134, column 2, line 3; page 135, column I, paragraph 3, line 3; page 135, column 2, paragraph 3, line 14.These alterations substantially change the conclusions of the article, which are as follows: the presence of a single copy RBM gene in American and Australian marsupials suggests that RBM was originally present as a single copy on the Y chromosome of an ancestral therian mammal. Following the divergence of marsupials and eutherians approximately 130 million years ago, RBM has been amplified independently in several marsupial and eutherian lineages. The conserved testis-specific expression of RBM in both marsupials and eutherians suggests that the selection for a critical male-specific function ensured the retention of RBM on the mammalian Y chromosome.Nature Genetics regrets any confusion this might have caused.Promoter swapping between the genes for a novel zinc finger protein and ~-catenin in pleiomorphic adenomas with t(3;8)(p21 ;q 12) translocations Nature Genetics 15, 170-174 (1997).Two lines of the Pl.AG I sequence (nt 5300-5621) in the 3' untranslated region were inadvertently deleted from Fig. 2 a. The complete sequence for this region can be obtained from GenBank accession nwnber U65002. We apologize for any inconvenience created by this error.

Holt-Oram syndrome is characterized by upper limb malformations and cardiac septation defects. Here, we demonstrate that mutations in the human TBX5 gene underlie this disorder. TBX5 was cloned from the disease locus on human chromosome 12q24.1 and identified as a member of the T-box transcription factor family. A nonsense mutation in TBX5 causes Holt-Oram syndrome in affected members of one family; a TBX5 missense mutation was identified in affected members of another. We conclude that TBX5 is critical for limb and heart development and suggest that haploinsufficiency of TBX5 causes Holt-Oram syndrome.

Mutations in a gene on chromosome 12q2 can produce a wide range of disease phenotypes characteristic of the Holt-Oram syndrome. This gene has an important role in both skeletal and cardiac development.

Using echocardiography, we identified 21 patients with a syndrome that included severe concentric cardiac hypertrophy, a small left ventricular cavity, and supernormal indexes of systolic function without concurrent medical illness or ischemic heart disease. Thirteen of the patients presented with dyspnea or chest pain. All patients studied had a history of hypertension and were compared with normotensive controls matched for age and sex. The patients were elderly (mean age, 73.3 years), predominantly female (16 patients), and mostly black (15 patients). Their cardiac function was characterized by excessive left ventricular emptying (ejection fraction on two-dimensional echocardiography [patients vs. controls], 79 +/- 4 vs. 59 +/- 5 per cent, P less than 0.001) and abnormal diastolic function as manifested by a prolonged early diastolic filling period (279 +/- 25 vs. 160 +/- 45 msec, P less than 0.001) and reduced peak diastolic dimension increase (11 +/- 4 vs. 16 +/- 5 cm per second, P less than 0.05). In spite of the clinical presentation of heart failure, all of 9 patients receiving either beta-receptor antagonists or calcium-channel blocking agents obtained symptomatic relief, whereas 6 of 12 patients receiving vasodilator medications had severe hypotensive reactions, including one death. We conclude that this unique subset of hypertensive patients has a clinical syndrome that warrants recognition and tailored management.

Transcripts of beta cardiac myosin heavy-chain gene can be detected in blood lymphocytes and used to screen for mutations that cause familial hypertrophic cardiomyopathy. This approach makes practical the identification of mutations responsible for this disorder and may be applicable to other diseases in which direct analysis is difficult because the mutated gene is expressed only in certain tissues. Preclinical or prenatal screening in an affected family will make it possible to study the disease longitudinally and to develop preventive interventions.