Abstract
MEN II A was described by Sipple 3 decades ago. Since then its autosomal dominant nature has been well established, usually presenting first with medullary thyroid carcinoma (MTC), whose C cells produce calcitonin. Hyperparathyroidism and pheochromocytomas complete the triad. Most reports are among White Caucasian patients, especially in Europe. Our experience suggests that MEN II A is uncommon among African Americans. For the past 22 years we have studied the kindred whose propositus (II-1) had MTC and whose mother (I-4) had the complete triad when recalled for medical check up. She had 12 children, 6 of which were diagnosed with MTC via elevated TCT levels. Seven out of 12 have undergone MTC removal and Hyperparathyroidism, while Pheochromocytomas have been identified in 3 out of 12. We wanted to established whether the same cysteine-rich region of exons 10-11 in the RET oncogene were responsible, or whether this African American family had mutations in other exons, such as exon 15. By DNA sequencing of PCR products of the exon 10 and 11 regions of the RET gene in this kindred we were able to identify one previously unknown exon 10 mutation, an Asp→Asn mutation in codon 624. Most of the previously reported ret gene mutations associated with MEN II A are located in the amino acid 609-635 region, of the ret protein, including the mutation found in this kindred. This extracellular region of the ret protein has been implicated in >90% of the studies of affected MEN II A families. MEN II A kindreds of African American origin might have unusual point mutations in the RET gene. This could have clinical relevance in screening young members of such families in order to prompt early therapeutic intervention. We acknowledge financial support from the NIH-RCMI-G12RR03051, NIH-MBRS S06GM08224 and the UPR School of Medicine.
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Cadilla, C., Vázquez, G., Alcántra, A. et al. New point mutation in the RET oncogene among an African American kindred with MEN II-A in Puerto Rico. Genet Med 1, 73 (1999). https://doi.org/10.1097/00125817-199901000-00125
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DOI: https://doi.org/10.1097/00125817-199901000-00125