遗传疾病和遗传报告杂志

A Case of MEN2A Associated with a C634R De-novo Mutation of the RET Gene at Algiers

Ammar Chikouche, Nadia Ould Bessi, Nawal Habak and Mebarek Boudissa

Introduction
Multiple endocrine neoplasia type 2A (MEN2A) is characterized by the association of medullary thyroid carcinoma (MTC) with pheochromocytoma and hyperparathyroidism. MEN2A represents 60% of MEN2 which is also subdivided into MEN2B (5%) and medullary thyroid cancer of the family (FMTC) which represents 35%. MEN2A is a rare hereditary disease, with autosomal dominant inheritance. Specific mutations of the RET protooncogene are associated with this disease.

Case Presentation and methods

The index case was an 18-year-old female patient with medullary thyroid cancer, without other clinical abnormalities. A blood sample taken from an EDTA tube was sent to the molecular biology laboratory accompanied by a request for genotypic analysis of the RET gene. A family pedigree was established and a consent form for DNA analysis was signed by the index case, his parents and his sister. DNA extraction was performed by the salt method. The genetic study concerned exon 11. It was carried out by amplification of the exon by polymerase chain reaction (PCR), followed by sequencing on ABI 3130 Applied Biosystems®. After finding the mutation in the index case; this mutation has been searched in relatives, including father, mother and sister.

Results and Discussion

The index case carried a mutation in exon 11 of the RET protooncogene. This mutation causes the replacement of cysteine at codon 634 with an arginine (C634R). The apparently healthy father; mother and only sister did not carry the mutation. C634R mutation has been described and found specifically in cases of MEN2A. This is why; the search for a pheochromocytoma should be carried out as well as a biological and medical monitoring. Only the clinically affected patient is a carrier of the RET gene mutation. Neither the father, the mother, nor the sister are carriers of it. This means that this C634R mutation is de novo.

Conclusion

Our work found a de novo mutation specific to MEN2A, which allows us to reassure parents and to provide a clinical and biological care and genetic counseling for the index case. The genetic study will be done only for his children.