Hereditary persistence of α-fetoprotein is due to both proximal and distal hepatocyte nuclear factor-1 site mutations 1 1The authors thank Dr. A. Chauchereau for the gift of A9TKCAT vector, Dr. O. Lahuna for helpful discussion, C. Aumas for excellent technical assistance, and S. Wenk for careful English proofreading of the text. We are grateful for the cooperation of the patients and their families.

Persistent α-Fetoprotein Elevation in Healthy Adults and Mutational Analysis of α-Fetoprotein Promoter, Enhancer, and Silencer Regions

“…Three families with HPAFP however do not have these reported mutations within the AFP promoter. Furthermore, AFP1 and his relatives represent a HPAFP case with neither of the two mutations (a −119 G>A substitution and a −55 C>A substitution) previously reported in the AFP promoter of HPAFP families 6. This supports the heterogeneous etiology of HPAFP.…”

“…As summarized in Table 3, six cases revealed mutations located at HNF-1 binding sites within the promoter region of the AFP gene (promoter positions −119 and −55). By increasing binding affinity, these mutations increase AFP transcription 6. Three families with HPAFP however do not have these reported mutations within the AFP promoter.…”

“…HPAFP, a benign, autosomal dominant condition may be caused by a mutation in the AFP promoter region that increases hepatocyte nuclear factor 1 (HNF-1) binding affinity, raising AFP transcription levels 6. To our knowledge, there have been only 20 cases of HPAFP reported, and among them, nine cases have conducted mutational analysis of the AFP promoter region.…”

“…Primers used for each section are listed in Table 1. Polymerase chain reaction (PCR) conditions were adapted from a previous report 6. Briefly, the reaction solution included 100 ng of DNA, 0.1 μmol/L of each primer, 2.5 U Taq DNA polymerase, 1×PCR buffer, and 200 μmol/L of each deoxynucleotide triphosphate (Taq, PCR buffer, and deoxynucleotide triphosphate from i-StarTaq TM DNA polymerase; iNtRON Biotechnology, Seongnam, Korea) for a total of 50 μL.…”

“…HPAFP is a rare, benign condition in which AFP elevation is persistent without any clinical abnormality, and it is inherited in an autosomal, dominant fashion. Until now, there have been 20 reported cases of HPAFP in the literature, and six of these were linked to two mutations in AFP promoter region: a −119 G>A substitution and a −55 C>A substitution 3–6. However, some families with HPAFP remain mutation-free for the promoter region, suggesting that other factors such as enhancer or silencer regions of AFP gene may contribute to AFP elevation 7–9…”