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Double Heterozygosity of BRCA2 and STK11 in Familial Breast Cancer Detected by Exome Sequencing.

Ataei-Kachouei M, Nadaf J, Akbari MT, Atri M, Majewski J, Riazalhosseini Y, Garshasbi M - Iran. J. Public Health (2015)

Bottom Line: We applied exome sequencing as a useful approach in heterogeneous diseases gene identification in present study for familial breast cancer.Sanger sequencing was applied for validation and segregation analysis of mutations.These mutations are inherited from their normal father.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

ABSTRACT

Background: Germ-line mutations of BRCA1 and BRCA2 genes are responsible for approximately 25-30% of dominantly inherited familial breast cancers; still a big part of genetic component is unknown. The aim of this study was to investigate genetic causes of familial breast cancer in a pedigree with recessive pattern of inheritance.

Methods: We applied exome sequencing as a useful approach in heterogeneous diseases gene identification in present study for familial breast cancer. Sanger sequencing was applied for validation and segregation analysis of mutations.

Results: Here, we describe a family with three affected sisters of early-onset invasive ductal carcinoma due to heterozygous frame shift mutation rs80359352 in BRCA2 gene as the first report in Iranian patients in association with a novel missense SNP of STK11 (p.S422G). These mutations are inherited from their normal father.

Conclusion: Despite apparent recessive pattern of inheritance a dominant gene (here BRCA2) can be involved in pathogenesis of hereditary breast cancer which can be explained by incomplete penetrance of BRCA2 mutations.

No MeSH data available.


Related in: MedlinePlus

Sanger sequencing of normal homozygous sibling and heterozygous patient for BRCA2 mutation with forward and reverse primers
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Figure 2: Sanger sequencing of normal homozygous sibling and heterozygous patient for BRCA2 mutation with forward and reverse primers

Mentions: Whole Exome Sequencing revealed, a 4bp frameshift deletion (BRCA2:NM_000059:exon11-:c.2808_2811del:p.936_937del) at position chr13:32-911297 that results in the insertion of 20 novel amino acids before a premature stop codon. Sanger sequencing confirmed that the three affected sisters and their father shared the same mutation which has been shown in Fig.2. In addition we identified a novel missense heterozygous missense variant p.S422G in STK11 gene. This latter variant is predicted to be benign by Polyphen-2 but it segregates along with BRCA2 mutation in the family.


Double Heterozygosity of BRCA2 and STK11 in Familial Breast Cancer Detected by Exome Sequencing.

Ataei-Kachouei M, Nadaf J, Akbari MT, Atri M, Majewski J, Riazalhosseini Y, Garshasbi M - Iran. J. Public Health (2015)

Sanger sequencing of normal homozygous sibling and heterozygous patient for BRCA2 mutation with forward and reverse primers
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4644579&req=5

Figure 2: Sanger sequencing of normal homozygous sibling and heterozygous patient for BRCA2 mutation with forward and reverse primers
Mentions: Whole Exome Sequencing revealed, a 4bp frameshift deletion (BRCA2:NM_000059:exon11-:c.2808_2811del:p.936_937del) at position chr13:32-911297 that results in the insertion of 20 novel amino acids before a premature stop codon. Sanger sequencing confirmed that the three affected sisters and their father shared the same mutation which has been shown in Fig.2. In addition we identified a novel missense heterozygous missense variant p.S422G in STK11 gene. This latter variant is predicted to be benign by Polyphen-2 but it segregates along with BRCA2 mutation in the family.

Bottom Line: We applied exome sequencing as a useful approach in heterogeneous diseases gene identification in present study for familial breast cancer.Sanger sequencing was applied for validation and segregation analysis of mutations.These mutations are inherited from their normal father.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

ABSTRACT

Background: Germ-line mutations of BRCA1 and BRCA2 genes are responsible for approximately 25-30% of dominantly inherited familial breast cancers; still a big part of genetic component is unknown. The aim of this study was to investigate genetic causes of familial breast cancer in a pedigree with recessive pattern of inheritance.

Methods: We applied exome sequencing as a useful approach in heterogeneous diseases gene identification in present study for familial breast cancer. Sanger sequencing was applied for validation and segregation analysis of mutations.

Results: Here, we describe a family with three affected sisters of early-onset invasive ductal carcinoma due to heterozygous frame shift mutation rs80359352 in BRCA2 gene as the first report in Iranian patients in association with a novel missense SNP of STK11 (p.S422G). These mutations are inherited from their normal father.

Conclusion: Despite apparent recessive pattern of inheritance a dominant gene (here BRCA2) can be involved in pathogenesis of hereditary breast cancer which can be explained by incomplete penetrance of BRCA2 mutations.

No MeSH data available.


Related in: MedlinePlus