Korean J Otolaryngol-Head Neck Surg.  2007 Jun;50(6):529-536.

Analysis of RET Gene Point Mutation in a Family with Multiple Endocrine Neoplasia Type 2A

• Kim SW
• Lee KD
• Kim JY
• Moon HS
• Kim YR
• Park YH
• Lee KS

Abstract

BACKGROUND AND OBJECTIVES: Multiple Endocrine Neoplasia type 2A (MEN 2A) is a syndrome that encompasses medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. Since MEN 2A is inherited as autosomal dominant, early detection and treatment is crucial. A genetic analysis of RET proto-oncogene of the family members of an index patient diagnosed as MEN 2A is reported.
SUBJECTS AND METHOD
A patient diagnosed as MEN 2A and his 13 family members across two generations were studied. Initially, DNA was extracted from the peripheral blood leukocyte of family members and PCR amplification of exons 10, 11, 13, 14, 15, and 16 was performed, followed by investigation of point mutation on the RET proto-oncogene using a DNA sequence analyzer. Cervical ultrasonography was carried out in the 3 nephews who were revealed to have RET proto-oncogene point mutation.
RESULTS
Point mutations of TGC (cys) to TGG (Trp) at codon 634 of exon 11 at RET proto-oncogene was detected by using automatic DNA sequence analyzing method in the index patient. The same point mutation was identified in 7 of the 13 family members. Cervical ultrasonography revealed bilateral thyroid nodules in all 3 nephews who had point mutations of RET proto-oncogene.
CONCLUSION
With the genetic analysis of RET proto-oncogene, limitations of the conventional calcitonin stimulation test may be overcome, and a more complete approach can be achieved through early diagnosis by carrying out this screening test for point mutations in family members of the patient with MEN 2A.

Keyword

MEN 2A; Medullary thyroid carcinoma; RET proto-oncogen; Point mutation

MeSH Terms

Base Sequence
Calcitonin
Codon
DNA
Early Diagnosis
Exons
Family Characteristics
Humans
Hyperparathyroidism
Leukocytes
Mass Screening
Multiple Endocrine Neoplasia Type 2a*
Multiple Endocrine Neoplasia*
Pheochromocytoma
Point Mutation*
Polymerase Chain Reaction
Proto-Oncogenes
Thyroid Neoplasms
Thyroid Nodule
Ultrasonography
Calcitonin
Codon
DNA