Prevalence and spectrum of mutations in the sarcomeric troponin T and I genes in a cohort of Spanish cardiac hypertrophy patients

García-Castro, Mónica; Reguero, Julián R.; Morı́s, César; Alonso-Montes, Cristina; Berrazueta, José R.; Sainz, Rocío; Álvarez, Victoria; Coto, Eliécer

doi:10.1016/j.ijcard.2006.08.049

Cited by 10 publications

(6 citation statements)

References 11 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, HRM population study of exon 14 of TNNT2 gene in 200 chromosomes from healthy control Caucasian Portuguese individuals, allow us to find this allele (rs3730238) in 3 chromosomes from control individuals (1.5%) (Figure 5f and 5g). This SNP has also been found in more European populations, namely in Spanish and French individuals [18,30,31]. Interestingly, it has not been described in more geographically distant populations, such as the Indian population [32].…”

Section: Resultsmentioning

confidence: 98%

High resolution melting: improvements in the genetic diagnosis of hypertrophic cardiomyopathy in a Portuguese cohort

et al. 2012

View full text Add to dashboard Cite

BackgroundHypertrophic Cardiomyopathy (HCM) is a complex myocardial disorder with a recognized genetic heterogeneity. The elevated number of genes and mutations involved in HCM limits a gene-based diagnosis that should be considered of most importance for basic research and clinical medicine.MethodologyIn this report, we evaluated High Resolution Melting (HRM) robustness, regarding HCM genetic testing, by means of analyzing 28 HCM-associated genes, including the most frequent 4 HCM-associated sarcomere genes, as well as 24 genes with lower reported HCM-phenotype association. We analyzed 80 Portuguese individuals with clinical phenotype of HCM allowing simultaneously a better characterization of this disease in the Portuguese population.ResultsHRM technology allowed us to identify 60 mutated alleles in 72 HCM patients: 49 missense mutations, 3 nonsense mutations, one 1-bp deletion, one 5-bp deletion, one in frame 3-bp deletion, one insertion/deletion, 3 splice mutations, one 5'UTR mutation in MYH7, MYBPC3, TNNT2, TNNI3, CSRP3, MYH6 and MYL2 genes. Significantly 22 are novel gene mutations.ConclusionsHRM was proven to be a technique with high sensitivity and a low false positive ratio allowing a rapid, innovative and low cost genotyping of HCM. In a short return, HRM as a gene scanning technique could be a cost-effective gene-based diagnosis for an accurate HCM genetic diagnosis and hopefully providing new insights into genotype/phenotype correlations.

show abstract

Section: Resultsmentioning

confidence: 98%

High resolution melting: improvements in the genetic diagnosis of hypertrophic cardiomyopathy in a Portuguese cohort

et al. 2012

View full text Add to dashboard Cite

show abstract

“…The above scenario is very similar to that of the relatively rare familial cardiomyopathies [14][15][16][17][18][19][20][21][22]. Approximately half of the kindreds with inherited CM have been shown to have mutations in genes encoding the sarcomeric proteins involved in the formation of the myofibrillar contractile unit in cardiomyocytes [14][15][16][17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 87%

“…Approximately half of the kindreds with inherited CM have been shown to have mutations in genes encoding the sarcomeric proteins involved in the formation of the myofibrillar contractile unit in cardiomyocytes [14][15][16][17][18][19][20][21][22]. Changes observed include insertions, deletions, and base changes in both introns and exons and, in the latter, both synonymous and nonsynonymous variations.…”

Section: Introductionmentioning

confidence: 99%

A Comparison between High Frequency Positive Pressure Ventilation and Intermittent Positive Pressure Ventilation during Closed Mitral Valvotomy

Mageed¹,

Shorrab²,

El-Tahan³

et al. 2007

IJA

View full text Add to dashboard Cite

Seventeen chemotherapy-induced cardiomyopathy (CM) patients and 100 volunteer blood donors (VBD) were analyzed for genetic variability in the following sarcomeric protein genes: cardiac alpha actin (ACTC); myosin light chain 2 (MYL2); myosin light chain 3 (MYL3); myosin heavy chain 7 (MYH7); myosin binding protein C3 (MYBPC3); tropomyosin 1 (TPM1); cardiac troponin I (TNNI3); and cardiac troponin T (TNNT2). No previously published mutations associated with familial CM were found in any of the subjects. No differences in the subjects and the published literature were found in the ACTC, MYL2, or TNNI3 genes. However, eight single nucleotide polymorphisms were identified in the other genes analyzed: a base change in intron 1a of TPM1; a synonymous change in exon 4 of TPM1; a base change in intron 11 of TNNT2; base changes in introns 2 and 4 of MYL3; a base change in introns 8 and 11 of MYH7; and a synonymous change in exon 31 of MYPC3. Both homozygous and heterozygous genotypes for each of these areas were identified among the subjects. Certain genotypes occurred more frequently in the CM patients and were deemed to be "skewed", with the MYH7I8 (TT) genotype approaching statistical significance (p = 0.052). Eighty-eight percent of the CM patients had one or more "skewed" genotypes, while only 64 percent of the VBD had this genetic pattern (p = 0.032). An increasing number of "skewed" genotypes was significantly associated with cardiomyopathy. Certain genotypes did not occur at all among the CM patients, and theoretically may confer protection against chemotherapy induced toxicity. Only one subject, a woman who developed CM on trastuzumab, had the genotype MYL3I2 (T/T), MYL3I4 (C/C), MYH7I11 (CC). Additional in vitro and clinical studies are warranted to understand the phenotypic, physiologic, and clinical significances of these variabilities in the sarcomeric protein genes.

show abstract

“…Por otra parte, los individuos con variantes patogénicas que afectan a filamentos gruesos sufrieron mayor obstrucción del tracto de salida del ventrículo izquierdo debido a un crecimiento pronunciado de dicha pared ventricular 11 . En otro estudio, en el que se analizaron nueve genes en 197 casos índice de MCH (incluidos 172 casos familiares y 25 aparentemente esporádicos), Richard, et al 107 encontraron variantes patogénicas en el 63% de los casos; de éstos, 42% se encontraba en la secuencia del gen MYBPC3 y 40% en MYH7 7 Ambos genes codifican a proteínas de filamentos gruesos y cabe señalar que este tipo de hallazgos se repite a través de diversas investigaciones 108,109 en distintos grupos étnicos. Lo anterior convierte a los genes MYBPC3 y MYH7 como el principal objeto de estudio ante casos de MCH con antecedente de muerte súbita familiar o paro cardíaco no letal (Tabla 2).…”

Section: Alteraciones En Miofilamentos Gruesos Y Delgadosunclassified

“…Hasta la fecha se han documentado más de 350 variantes patogénicas en el gen MYH7 en HGMD, con fenotipos clínicos altamente variables, como es el estudio de cohorte de García-Castro, et al 108 en 120 pacientes no emparentados con MCH. A los sujetos de este estudio se les realizó historia clínica y estudio molecular, y se identificaron 31 variantes patogénicas distintas en 32 pacientes, 8% de los cuales (10 pacientes) tenía alteración en el gen MYH7; la media de edad a la que se estableció el diagnóstico fue de 35 años y 3 de estos 10 pacientes (70%) tenían el antecedente familiar de MCH 108 .…”

Section: El Gen Myh7 Y Su Papel En La Mchunclassified

Genes frecuentemente asociados con muerte súbita en miocardiopatía hipertrófica primaria

Herrera-Rodríguez

Totomoch-Serra

Rosas-Madrigal

et al. 2020

ACM

View full text Add to dashboard Cite

show abstract

Prevalence and spectrum of mutations in the sarcomeric troponin T and I genes in a cohort of Spanish cardiac hypertrophy patients

Cited by 10 publications

References 11 publications

High resolution melting: improvements in the genetic diagnosis of hypertrophic cardiomyopathy in a Portuguese cohort

High resolution melting: improvements in the genetic diagnosis of hypertrophic cardiomyopathy in a Portuguese cohort

A Comparison between High Frequency Positive Pressure Ventilation and Intermittent Positive Pressure Ventilation during Closed Mitral Valvotomy

Genes frecuentemente asociados con muerte súbita en miocardiopatía hipertrófica primaria

Contact Info

Product

Resources

About