Challenges and Applications of Genetic Testing in Dilated Cardiomyopathy: Genotype, Phenotype and Clinical Implications

Furquim, Silas Ramos; Linnenkamp, Bianca; Olivetti, Natália Quintella Sangiorgi; Giugni, Fernando Rabioglio; Lipari, Layara Fernanda Vicente Pereira; Andrade, Fernanda Almeida; Krieger, José Eduardo

doi:10.36660/abc.20230174

person Silas Ramos Furquim

Conception and design of the research · Acquisition of data · Writing of the manuscript · Critical revision of the manuscript for important intellectual content

schoolInstituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP – Brazil

0000-0001-8727-0940

person Bianca Linnenkamp

Conception and design of the research · Acquisition of data · Writing of the manuscript · Critical revision of the manuscript for important intellectual content

schoolInstituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP – Brazil

person Natália Quintella Sangiorgi Olivetti

Conception and design of the research · Acquisition of data · Analysis and interpretation of the data · Writing of the manuscript · Critical revision of the manuscript for important intellectual content

schoolInstituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP – Brazil

0000-0003-1061-8982

person Fernando Rabioglio Giugni

Critical revision of the manuscript for important intellectual content

schoolInstituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP – Brazil

person Layara Fernanda Vicente Pereira Lipari

Analysis and interpretation of the data · Writing of the manuscript · Critical revision of the manuscript for important intellectual content

schoolInstituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP – Brazil

person Fernanda Almeida Andrade

Analysis and interpretation of the data · Writing of the manuscript · Critical revision of the manuscript for important intellectual content

schoolInstituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP – Brazil

0000-0002-2612-8040

person José Eduardo Krieger

Conception and design of the research · Writing of the manuscript · Critical revision of the manuscript for important intellectual content

schoolInstituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP – Brazil

Mailing Address: Silas Ramos Furquim • Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – Av. Dr. Eneas de Carvalho Aguiar, 44. Postal Code 05403-900, São Paulo, SP – Brazil E-mail: silasfurquim@hotmail.com

Potential conflict of interest

No potential conflict of interest relevant to this article was reported.

Editor responsible for the review: Gláucia Maria Moraes de Oliveira


Identify the name of the proband (patient under evaluation), date of birth, age of the proband during assessment, and date of evaluation.
Build the pedigree with information from at least three generations from the proband and include the proband's first-degree relatives (parents, siblings, and offspring) and second-degree relatives (grandparents, uncles and aunts, nephews and nieces and grandchildren).
Indicate the proband's place of origin and family ancestry, in addition to asking whether there is known consanguinity in the family. Consanguinity is not always known; however, this possibility should be suspected when the parents are from a city with few inhabitants.
Identify known diseases and other findings through captions.
Position older individuals to the left and younger individuals to the right.
Indicate the age and cause of death of deceased individuals.
Number generations using Roman numerals to facilitate the identification of individuals in the family.
Signal individuals who have undergone genetic testing and indicate the result.

Gene	Frequency	Gene	Frequency	Gene	Frequency
TTN	18-25%	MYBPC3	2%	DES	<1%
DSG2	4–15%	FLNC	0–3%	TMEM43	<1%
DSP	1-13%	ACTC1	<1%	TAZ	Unknown
PLN	0–12%	LDB3	<1%	BAG3	Unknown
LMNA	6%	TNNC1	<1%	RBM20	Unknown
MYH6	4%	TNNI3	<1%	DSC2	Unknown
MYH7	4%	TNNT2	<1%	DMD	Unknown
SCN5A	0–2%	TPM1	<1%	EMD	Unknown

Predictors of positive genetic test
Skeletal myopathy	1 point
Family history of DCM	1 point
Low voltage ECG	1 point
Absence of hypertension	1 point
Absence of LBBB	1 point
Score: 0 to 5 points

Classification of pathogenicity	class	probability
Benign	class 1	< 5%
Likely Benign	class 2	< 10%
Variant of uncertain significance (VUS)	class 3	10 - 90%
Likely Pathogenic	class 4	> 90%
Pathogenic	class 5	> 95%

Gene	Protein	Region
LMNA	Lamin A/C	Nuclear envelope
RBM20	RNA-binding motif protein-20	Nucleus
PLN	Phospholamban	Sarcoplasmic reticulum
FLNC	Filamin C	Cytoskeleton
DES	Desmin	Cytoskeleton
DMD	Dystrohin	Cytoskeleton
TTN	Titin	Sarcomere
MYH7	Beta-cardiac/slow skeletal myosin heavy chain	Sarcomere
TNNT2	Troponin T2	Sarcomere
TPM1	Tropomyosin 1	Sarcomere
MYBPC3	Myosin-binding protein C 3	Sarcomere
SCN5A	Sodium channel, voltage-gated, type V, alpha subunit	Cell membrane

Age	0-5 years	6-12 years	13-19 years	20-50 years	>50 years
Periodicity of clinical evaluation	Yearly	1-2 years	1-3 years	2-3 years	5 years

Challenges and Applications of Genetic Testing in Dilated Cardiomyopathy: Genotype, Phenotype and Clinical Implications

Abstract