%0 Journal Article
%T Genotype-phenotype correlations in hypertrophic cardiomyopathy: a multicenter study in Portugal and Spain of the TPM1 p.Arg21Leu variant.
%A Lamounier Junior A
%A Guitián González A
%A Rodríguez Vilela A
%A Repáraz Andrade A
%A Rubio Alcaide Á
%A Berta Sousa A
%A Benito López C
%A Alonso García D
%A Fernández Ferro G
%A Cruz I
%A Cárdenas Reyes IJ
%A Salazar-Mendiguchía García J
%A Larrañaga-Moreira JM
%A Ochoa JP
%A Palomino-Doza J
%A de la Higuera Romero L
%A Nicolás Cicerchia M
%A Restrepo Córdoba MA
%A Peña-Peña ML
%A Noël Brögger M
%A Loureiro M
%A Mogollón Jiménez MV
%A Bilbao Quesada R
%A Franco Gutiérrez R
%A García Hernández S
%A Ripoll-Vera T
%A Fernández X
%A Azevedo O
%A García Pavía P
%A Lopes LR
%A Ortiz M
%A Brito D
%A Barriales-Villa R
%A Monserrat Iglesias L
%J Rev Esp Cardiol (Engl Ed)
%V 0
%N 0
%D Feb 2021 25
%M 33642254
暂无%R 10.1016/j.rec.2021.01.001
%X <B>OBJECTIVE: </B>TPM1 is one of the main hypertrophic cardiomyopathy (HCM) genes. Clinical information on carriers is relatively scarce, limiting the interpretation of genetic findings in individual patients. Our aim was to establish genotype-phenotype correlations of the TPM1 p.Arg21Leu variant in a serie of pedigrees.<BR><B>METHODS: </B>TPM1 was evaluated by next-generation sequencing in 10 561 unrelated probands with inherited heart diseases. Familial genetic screening was performed by the Sanger method. We analyzed TPM1 p.Arg21Leu pedigrees for cosegregation, clinical characteristics, and outcomes. We also estimated the geographical distribution of the carrier families in Portugal and Spain.<BR><B>RESULTS: </B>The TPM1 p.Arg21Leu variant was identified in 25/4099 (0.61%) HCM-cases, and was absent in 6462 control individuals with other inherited cardiac phenotypes (P<.0001). In total, 83 carriers (31 probands) were identified. The combined LOD score for familial cosegregation was 3.95. The cumulative probability of diagnosis in carriers was 50% at the age of 50 years for males, and was 25% in female carriers. At the age of 70 years, 17% of males and 46% of female carriers were unaffected. Mean maximal left ventricular wall thickness was 21.4 ±7.65mm. Calculated HCM sudden death risk was low in 34 carriers (77.5%), intermediated in 8 (18%), and high in only 2 (4.5%). Survival free of cardiovascular death or heart transplant was 87.5% at 50 years. Six percent of carriers were homozygous and 18% had an additional variant. Family origin was concentrated in Galicia, Extremadura, and northern Portugal, suggesting a founder effect.<BR><B>CONCLUSIONS: </B>TPM1 p.Arg21Leu is a pathogenic HCM variant associated with late-onset/incomplete penetrance and a generally favorable prognosis.