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Germline RET proto-oncogene mutations in two Taiwanese families with multiple endocrine neoplasia type 2A
Abstract:
To elucidate the germline RET proto-oncogene mutations in Taiwanese families with multiple endocrine neoplasia type 2A (MEN 2A), we extracted DNA from peripheral blood leukocytes of 28 members of two families with MEN 2A. Oligonucleotide primers for exons 10 and 11 were used to analyze the nucleotide sequence of codons 609, 611, 618, and 620 of exon 10, and codon 634 of exon 11 of the RET proto-oncogene. Two fragments of genomic DNA were amplified by polymerase chain reaction (PCR). The amplified PCR products were separated and purified from primers and free nucleotides in agarose gels, and the expected 187-bp and 234-bp bands were cut from the gels and sequenced. Thirteen family members in the two MEN 2A kindreds had mutations in codon 634 of exon 11. In kindred 1 (15 members available for this study), a heterozygous codon 634 mutation in nine members and a homozygous codon 634 mutation in one member led to the substitution of Phe (TTC) for Cys (TGC). Three members of kindred 2 (13 members available for this study) had a heterozygous base pair change in codon 634, which led to the substitution of Arg (CGC) for Cys (TGC). In this study, we found two mutation events occurring in two MEN 2A kindreds and also discovered a homozygous point mutation in one woman that led to heterozygous mutations in all of her children.
Insights
Germline RET proto-oncogene mutations were identified in Taiwanese families with multiple endocrine neoplasia type 2A (MEN 2A). Two distinct mutation events in codon 634 were found, including a rare homozygous mutation.
Area of Science:
- Genetics and Genomics
- Oncology
- Endocrinology
Background:
- Multiple Endocrine Neoplasia type 2A (MEN 2A) is a hereditary cancer syndrome.
- Germline mutations in the RET proto-oncogene are the primary cause of MEN 2A.
- Understanding specific mutation patterns is crucial for genetic counseling and early detection.
Purpose of the Study:
- To investigate germline RET proto-oncogene mutations in Taiwanese families affected by MEN 2A.
- To identify specific mutation sites and patterns within the RET gene in these families.
- To analyze the inheritance of identified mutations, including rare homozygous cases.
Main Methods:
- DNA was extracted from peripheral blood leukocytes of 28 family members across two MEN 2A kindreds.
- Oligonucleotide primers were used to amplify exons 10 and 11 of the RET proto-oncogene.
- Polymerase chain reaction (PCR) products were sequenced to analyze specific codons (609, 611, 618, 620, 634).
Main Results:
- Thirteen family members exhibited mutations in codon 634 of exon 11.
- Kindred 1 showed a heterozygous codon 634 mutation in nine members and a homozygous mutation in one, resulting in Phe (TTC) for Cys (TGC) substitution.
- Kindred 2 revealed heterozygous base pair changes in codon 634 in three members, leading to Arg (CGC) for Cys (TGC) substitution.
Conclusions:
- Two distinct RET proto-oncogene mutation events were identified in the two MEN 2A kindreds.
- A rare homozygous point mutation at codon 634 was discovered in one individual, with heterozygous transmission to her children.
- These findings contribute to the understanding of RET mutation heterogeneity in MEN 2A.