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Gender Differences in the Inheritance Mode of RYR2 Mutations in Catecholaminergic Polymorphic Ventricular Tachycardia Patients.

Ohno S, Hasegawa K, Horie M - PLoS ONE (2015)

Bottom Line: The inheritance of RYR2 mutations was significantly more frequent from mothers (n = 12, 34.3%) than fathers (n = 2, 5.7%) (P = 0.013).The mean ages of onset were not significantly different in probands between de novo mutations and those from mothers.These data would be useful for family analysis and risk stratification of the disease.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular and Respiratory Department, Shiga University of Medical Science, Otsu, Japan; Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan; Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.

ABSTRACT
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is one of the causes of sudden cardiac death in young people and results from RYR2 mutations in ~60% of CPVT patients. The inheritance of the RYR2 mutations follows an autosomal dominant trait, however, de novo mutations are often identified during familial analysis. In 36 symptomatic CPVT probands with RYR2 mutations, we genotyped their parents and confirmed the origin of the respective mutation. In 26 sets of proband and both parents (trio), we identified 17 de novo mutations (65.4%), seven from their mothers and only two mutations were inherited from their fathers. Among nine sets of proband and mother, five mutations were inherited from mothers. Four other mutations were of unknown origin. The inheritance of RYR2 mutations was significantly more frequent from mothers (n = 12, 34.3%) than fathers (n = 2, 5.7%) (P = 0.013). The mean ages of onset were not significantly different in probands between de novo mutations and those from mothers. Thus, half of the RYR2 mutations in our cohort were de novo, and most of the remaining mutations were inherited from mothers. These data would be useful for family analysis and risk stratification of the disease.

No MeSH data available.


Related in: MedlinePlus

Scheme for Mutation Inheritance.Showing the number of screened family members and the origin of RYR2 mutations. The boxes in the middle lane show genotyped family members in each group. Trio; proband and both parents, P-M; proband and mother, P-F; Proband and father.
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pone.0131517.g001: Scheme for Mutation Inheritance.Showing the number of screened family members and the origin of RYR2 mutations. The boxes in the middle lane show genotyped family members in each group. Trio; proband and both parents, P-M; proband and mother, P-F; Proband and father.

Mentions: The study cohort consisted of 36 Japanese CPVT probands (18 boys) with RYR2 mutations, their 62 parents and their 29 siblings. All the probands suffered syncope or cardiac pulmonary arrest (CPA) and were registered for genetic screening between 2005 and 2013 in Shiga University of Medical Science. Genetic analysis was performed after obtaining written informed consent in accordance with the study protocol approved by the Institutional Review Board of Shiga University of Medical Science. The approved number is 23–128. In the study protocol, we included the statement that the research results would be published with anonymized clinical information. If the participants were minors or children, we obtained the informed consent verbally from them and written consent from their guardians. The verbal consent was recorded in the clinical record, and our Institutional Review Board approved to obtain written consent from their guardians. According to the participating family members, we divided them into three groups: 26 sets of proband and both parents (trio), 9 sets of proband and mother (P-M) and 1 sets of proband and father (P-F) (Fig 1). All the participating parents were also genotyped, and the origin of the mutation was classified into four groups: de novo, from mother, from father and unknown. Their consanguinity of de novo group were confirmed by screening of 15 single nucleotide polymorphisms and 1 microsatellite. The unknown group included the case where the inheritance mode could not be determined due to the non-participation of either one of their parents. We evaluated the clinical and genetic characteristics of the probands and compared them in two groups: de novo and maternal origin. The mutation locations were classified into three groups based on the previous report [11]. In 23 trio families, we compared the age of parents at the birth of the probands in three groups: de novo, maternally- and paternally originated mutations.


Gender Differences in the Inheritance Mode of RYR2 Mutations in Catecholaminergic Polymorphic Ventricular Tachycardia Patients.

Ohno S, Hasegawa K, Horie M - PLoS ONE (2015)

Scheme for Mutation Inheritance.Showing the number of screened family members and the origin of RYR2 mutations. The boxes in the middle lane show genotyped family members in each group. Trio; proband and both parents, P-M; proband and mother, P-F; Proband and father.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482545&req=5

pone.0131517.g001: Scheme for Mutation Inheritance.Showing the number of screened family members and the origin of RYR2 mutations. The boxes in the middle lane show genotyped family members in each group. Trio; proband and both parents, P-M; proband and mother, P-F; Proband and father.
Mentions: The study cohort consisted of 36 Japanese CPVT probands (18 boys) with RYR2 mutations, their 62 parents and their 29 siblings. All the probands suffered syncope or cardiac pulmonary arrest (CPA) and were registered for genetic screening between 2005 and 2013 in Shiga University of Medical Science. Genetic analysis was performed after obtaining written informed consent in accordance with the study protocol approved by the Institutional Review Board of Shiga University of Medical Science. The approved number is 23–128. In the study protocol, we included the statement that the research results would be published with anonymized clinical information. If the participants were minors or children, we obtained the informed consent verbally from them and written consent from their guardians. The verbal consent was recorded in the clinical record, and our Institutional Review Board approved to obtain written consent from their guardians. According to the participating family members, we divided them into three groups: 26 sets of proband and both parents (trio), 9 sets of proband and mother (P-M) and 1 sets of proband and father (P-F) (Fig 1). All the participating parents were also genotyped, and the origin of the mutation was classified into four groups: de novo, from mother, from father and unknown. Their consanguinity of de novo group were confirmed by screening of 15 single nucleotide polymorphisms and 1 microsatellite. The unknown group included the case where the inheritance mode could not be determined due to the non-participation of either one of their parents. We evaluated the clinical and genetic characteristics of the probands and compared them in two groups: de novo and maternal origin. The mutation locations were classified into three groups based on the previous report [11]. In 23 trio families, we compared the age of parents at the birth of the probands in three groups: de novo, maternally- and paternally originated mutations.

Bottom Line: The inheritance of RYR2 mutations was significantly more frequent from mothers (n = 12, 34.3%) than fathers (n = 2, 5.7%) (P = 0.013).The mean ages of onset were not significantly different in probands between de novo mutations and those from mothers.These data would be useful for family analysis and risk stratification of the disease.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular and Respiratory Department, Shiga University of Medical Science, Otsu, Japan; Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan; Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.

ABSTRACT
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is one of the causes of sudden cardiac death in young people and results from RYR2 mutations in ~60% of CPVT patients. The inheritance of the RYR2 mutations follows an autosomal dominant trait, however, de novo mutations are often identified during familial analysis. In 36 symptomatic CPVT probands with RYR2 mutations, we genotyped their parents and confirmed the origin of the respective mutation. In 26 sets of proband and both parents (trio), we identified 17 de novo mutations (65.4%), seven from their mothers and only two mutations were inherited from their fathers. Among nine sets of proband and mother, five mutations were inherited from mothers. Four other mutations were of unknown origin. The inheritance of RYR2 mutations was significantly more frequent from mothers (n = 12, 34.3%) than fathers (n = 2, 5.7%) (P = 0.013). The mean ages of onset were not significantly different in probands between de novo mutations and those from mothers. Thus, half of the RYR2 mutations in our cohort were de novo, and most of the remaining mutations were inherited from mothers. These data would be useful for family analysis and risk stratification of the disease.

No MeSH data available.


Related in: MedlinePlus