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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

Sequence Electropherograms of Patient 15.Sequence electropherogram of control (upper), patient 15 (middle) and his father (bottom). The peak of the mutant ā€˜aā€™ allele in 7024 residue (red arrow) was lower than the original ā€˜gā€™ peak in the sequence electropherogram of the father, which suggested the presence of mosaicism.
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pone.0131517.g002: Sequence Electropherograms of Patient 15.Sequence electropherogram of control (upper), patient 15 (middle) and his father (bottom). The peak of the mutant ā€˜aā€™ allele in 7024 residue (red arrow) was lower than the original ā€˜gā€™ peak in the sequence electropherogram of the father, which suggested the presence of mosaicism.

Mentions: In 26 mutations identified in 26 probands of the trio group, 17 RYR2 mutations were confirmed to be de novo, seven mutations were from their mothers and two from their fathers. (Fig 1 and Table 1). One of the fathers (patient 15) was suspected to carry the mutation in mosaicism (Fig 2). Five mutations from nine mutations in the P-M group were inherited from their mothers, and four were unknown origin; de novo or from their fathers. Although four fathers in the P-M group did not agree to the genetic analysis, they were all healthy and had no history of syncope or cardiac arrest. The mother and maternal grandmother of patient 26 (Table 1) died suddenly at a young age, and his sister carried the same mutation. Accordingly, the mutation appeared to come from his mother side, but we failed to obtain their maternal genomic information. Therefore, his mutation was consequently classified as unknown origin.


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

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

Sequence Electropherograms of Patient 15.Sequence electropherogram of control (upper), patient 15 (middle) and his father (bottom). The peak of the mutant ā€˜aā€™ allele in 7024 residue (red arrow) was lower than the original ā€˜gā€™ peak in the sequence electropherogram of the father, which suggested the presence of mosaicism.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131517.g002: Sequence Electropherograms of Patient 15.Sequence electropherogram of control (upper), patient 15 (middle) and his father (bottom). The peak of the mutant ā€˜aā€™ allele in 7024 residue (red arrow) was lower than the original ā€˜gā€™ peak in the sequence electropherogram of the father, which suggested the presence of mosaicism.
Mentions: In 26 mutations identified in 26 probands of the trio group, 17 RYR2 mutations were confirmed to be de novo, seven mutations were from their mothers and two from their fathers. (Fig 1 and Table 1). One of the fathers (patient 15) was suspected to carry the mutation in mosaicism (Fig 2). Five mutations from nine mutations in the P-M group were inherited from their mothers, and four were unknown origin; de novo or from their fathers. Although four fathers in the P-M group did not agree to the genetic analysis, they were all healthy and had no history of syncope or cardiac arrest. The mother and maternal grandmother of patient 26 (Table 1) died suddenly at a young age, and his sister carried the same mutation. Accordingly, the mutation appeared to come from his mother side, but we failed to obtain their maternal genomic information. Therefore, his mutation was consequently classified as unknown origin.

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