Hereditary Persistence Of Alpha-fetoprotein Research Articles

Hereditary Persistence Of Alpha-fetoprotein: A Rare Entity From A Primary Care Center In Bangladesh

Hereditary persistence of alpha- fetoprotein (HFAFP) is a rare benign autosomal dominant disorder.Here we report a case of 15 years old boy who was found to have elevated alpha-fetoprotein during her routine evaluation for gynaecomastia. All other common possibilities for raised alpha-fetoprotein were excluded.Subsequently, 2 of his family members were found to have raised alpha-fetoprotein.One is his father and another one is his brother.Raised alpha-fetoprotein has a wide differential diagnosis including, pregnancy, germ cell tumors, hepatocellular carcinoma and others.But after exclusion of other possibilities, persisting elevated alphafetoprotein raises the suspicion for HPAFP.Testing other family members for AFP and specific genetic study aid in diagnosis. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 216-217

Hereditary Persistence of Alpha Fetoprotein in an Indian Family

Hereditary Persistence of Alpha Fetoprotein in an Indian Family

Hereditary persistence of alpha-fetoprotein mimicking testicular cancer in a patient with acute epididymitis

Only a few cases of hereditary persistence of α-fetoprotein (HPAFP) have been published. This report presents an association between HPAFP and inflammatory testis disease, to the authors' knowledge, for the first time. HPAFP was diagnosed in a 41-year-old patient with acute epididymitis after exclusion of malignancies and benign diseases.

High Alpha-Fetoprotein Persistence after Orchiectomy. On a Case of Uncommon Etiology

Background The following report describes a case of inherited elevation of alpha-fetoprotein (AFP) in a young male suspected for testicular cancer. AFP shows very high values during fetal life. After birth the synthesis of AFP decreases dramatically, and only trace amounts are detected in the adult. From this age on, serum AFP can rise above normal in some diseases, e.g. liver disorders, and in some kind of tumors. A condition in which persistent high levels of AFP are found, named Hereditary Persistence of AFP [HPAFP), was first reported in 1983 by Ferguson-Smith, and then recorded in the literature only on eleven occasions till 2004. The occurrence of HPAFP may be underestimated. HPAFP can be easily confirmed by testing AFP levels in blood-related family members. Methods An elevated serum AFP (about 20 μg/mL) was found in a 27–year-old white man with an unremarkable medical history, who was concerned to have left testicular cancer. By our examination, his left testis was markedly reduced in size. β-HCG, LDH, and liver function were normal. Surgical inguinal exploration with testis and spermatic cord excision was carried out. Postoperative repeated AFP levels remained persistently elevated, in the range from 20 to 30 μg/mL. Careful evaluation for occult cancer showed no abnormality. Histology showed necrotic tissue and could not make a reliable diagnosis. A literature search was done using PubMed by key word “alpha-fetoprotein” and “elevation”. Thinking of a hereditary trait, we decided to screen patient's blood-related family members. Results AFP was found to be elevated in another four out of six relatives within three generations, unrelated to any disease. This pedigree was consistent with an autosomal dominant inheritance pattern. Conclusions HPAFP could mislead the physician. Failure to recognize HPAFP can lead to unsuitable treatments. The existence of this clinically benign condition needs to be considered in both children and adults with unexplained and persistent elevation of AFP, e.g. those diagnosed or suspected for germ cell tumor.

Hereditary persistence of alpha‐fetoprotein

Hereditary persistence of alpha-fetoprotein (HPAFP) is a rare benign autosomal dominant disorder. Here we report a 7-year-old healthy female who was found to have elevated alpha-fetoprotein (AFP) of 55-88 ng/ml over a 2-year period. Subsequently, AFP was also determined to be elevated in another 4 out of 8 family members in three generations, consistent with an autosomal dominant inheritance pattern. Elevated AFP levels are usually related to pregnancy, congenital disorders, liver diseases, or specific malignancies. However, HPAFP should be considered in the differential diagnosis of children with unexplained elevation of AFP. This disorder can be easily confirmed by measuring AFP levels in family members or checking specific point mutations of AFP gene promoter.

Molecular mechanisms of hereditary persistence of α-fetoprotein (AFP) in two Japanese familiesA hepatocyte nuclear factor-1 site mutation leads to induction of the AFP gene expression in adult livers

alpha-Fetoprotein (AFP) is produced abundantly in fetal liver but is hardly detectable in adults. In this study, we investigated two unrelated Japanese families with hereditary persistence of AFP. A g-->a substitution at nucleotide -119 (-119g-->a) in the hepatocyte nuclear factor (HNF)-1 binding site of the AFP promoter was identified in both families. The activity of the wild- or variant-type human AFP promoter was evaluated by in vitro and in vivo transfection experiments. This substitution in the AFP promoter significantly stimulated its transcriptional activity in human hepatoma cells, regardless of their prior AFP production. The variant-type AFP promoter was also active in adult mouse livers in vivo. Additionally, overexpression of HNF-1alpha stimulated the activity of both the wild- and variant-type AFP promoters in hepatoma cells. HNF-1alpha expression also activated both AFP promoters even in nonhepatoma cells, and this activation was suppressed by nuclear factor (NF)-I overexpression. These results indicate that an HNF-1 binding site mutation leads to induction of the AFP gene expression in adult liver, and suggest that competition between HNF-1 and NF-I in this region is involved in transcriptional regulation of the AFP gene during hepatic development.

Hereditary persistence of alpha-fetoprotein and H19 expression in liver of BALB/cJ mice is due to a retrovirus insertion in the Zhx2 gene.

The alpha-fetoprotein (AFP) and H19 genes are transcribed at high levels in the mammalian fetal liver but are rapidly repressed postnatally. This repression in the liver is controlled, at least in part, by the Afr1 gene. Afr1 was defined >25 years ago when BALB/cJ mice were found to have 5- to 20-fold higher adult serum AFP levels compared with all other mouse strains; subsequent studies showed that this elevation was due to higher Afp expression in the liver. H19, which has become a model for genomic imprinting, was identified initially in a screen for Afr1-regulated genes. The BALB/cJ allele (Afr1(b)) is recessive to the wild-type allele (Afr1(a)), consistent with the idea that Afr1 functions as a repressor. By high-resolution mapping, we identified a gene that maps to the Afr1 interval on chromosome 15 and encodes a putative zinc fingers and homeoboxes (ZHX) protein. In BALB/cJ mice, this gene contains a murine endogenous retrovirus within its first intron and produces predominantly an aberrant transcript that no longer encodes a functional protein. Liver-specific overexpression of a Zhx2 transgene restores wild-type H19 repression on a BALB/cJ background, confirming that this gene is responsible for hereditary persistence of Afp and H19 in the livers of BALB/cJ mice. Thus we have identified a genetically defined transcription factor that is involved in developmental gene silencing in mammals. We present a model to explain the liver-specific phenotype in BALB/cJ mice, even though Afr1 is a ubiquitously expressed gene.

Hereditary persistence of alphafetoprotein (HPAFP). A new case of G a substitution in the promoter region of the gene

Hereditary persistence of alphafetoprotein (HPAFP). A new case of G a substitution in the promoter region of the gene

La persistance héréditaire de lˈalpha-fœtoprotéine :à propos dˈun cas

Introduction. – Hereditary persistence of alpha-fetoprotein is a rare disorder which exists with no simultaneous disease. The tenth case in the world (two brothers with seminoma and their father) is documented and a complete literature review was done. Exegesis. – It is transmitted as an autosomal dominant; a disease point mutation has been identified. The failure to recognize hereditary persistence of alpha-fetoprotein sometimes involves unjustified treatments. Conclusion. – The occurrence of this situation is probably underestimated and it could explain residual levels of alpha-fetoprotein.

Hereditary persistence of α-fetoprotein: Case report and review of the literature

Persistently elevated alpha-fetoprotein (AFP) levels of 24 to 30 micrograms/ml (normal < 10 micrograms/ml) were found in a 38-year-old healthy man. Subsequently, AFP was found to be elevated in another five out of 13 family members within three generations. The pedigree is consistent with an autosomal dominant inheritance pattern. No discernible disease and no functional abnormality appears to be associated with this clinically benign disorder which has been recorded in the literature on four occasions to date. The reported AFP levels in these other cases ranged from 18 to 198 micrograms/ml. Physiologically, AFP is mainly produced in the liver and the yolk sac of human fetuses more than four weeks old, with peak values of up to 4 mg/ml at 12 to 16 weeks of gestation. After birth, AFP levels usually fall, within eight to 12 months, to a very low concentration of < 10 micrograms/ml and persist at low levels throughout life. However, AFP levels can rise above normal in both children and adults in distinct conditions and diseases which will be discussed. Hereditary persistence of alpha-fetoprotein (HPAFP) should be considered in both children and adults with unexplained and persistent elevation of AFP e.g., those screened for hepatocellular carcinoma or diagnosed for germ cell tumor. It should also be recognized in AFP screening for neural tube defects or Down's syndrome during pregnancy. Hereditary persistence of AFP can be easily confirmed by analyzing AFP levels in family members.

Hereditary persistence of alpha-fetoprotein

A proband with persistently elevated alpha-fetoprotein (AFP) levels ranging between 21–129 ng/ml with median of 90 ng/ml has been found and observed for 1 year. Family studies have revealed that his father had had persistent AFP elevation for 4 years, ranging from 46 to 198. 2 ng/ml, with median level of 93 ng/ml. His brother also has elevated AFP level. His mother, paternal uncle and paternal aunt, however have normal AFP level. Clinical examinations and laboratory tests have shown that AFP elevations are not associated with primary hepatocellular carcinoma, hepatitis, or other malignancies. We believe that such AFP persistency is hereditary. So far as we known, this is the first family of hereditary AFP persistence reported in China and the fourth one throughout the world.

A G-->A substitution in an HNF I binding site in the human alpha-fetoprotein gene is associated with hereditary persistence of alpha-fetoprotein (HPAFP).

A family displaying hereditary persistence of alpha-fetoprotein (HPAFP) in adult life was detected in an antenatal screening programme for spina bifida. RFLP linkage analysis shows that the trait is linked with the albumin-AFP locus. The molecular mechanism responsible for the post-natal repression of the AFP gene is unknown. We wished to determine the molecular mechanism underlying HPAFP in this family. Sequence analysis of the 5'-flanking sequences of their gene revealed a GA substitution at position -119 associated with the trait. This substitution occurs in a potential HNF I binding site, and increases the similarity of the sequence to a consensus HNF I recognition site. In a competitive gel retardation assay the mutant sequence binds HNF I alpha more tightly than the wild type sequence. Furthermore, 5'-flanking sequences of the human AFP gene containing the G-->A substitution direct a higher level of CAT expression in transfected human hepatoma cells than the wild type sequences. We conclude that the G-->A substitution at position -119 of the AFP gene is the mutation causing HPAFP in this family. These results highlight the importance of this HNF I binding site in the developmental regulation of the AFP gene.

Hereditary persistence of alpha-fetoprotein

Persistently elevated α-fetoprotein levels were found in a 43-yr-old man in the absence of any specific pathology. Elevated serum α-fetoprotein levels were subsequently found in three first-degree relatives, two siblings, and one daughter. This represents the third documented family with hereditary persistence of α-fetoprotein. The pedigree is consistent with an autosomal dominant inheritance. Such elevated α-fetoprotein levels may be difficult to interpret in patients being screened for malignancy or in maternal serum α-fetoprotein screening programs. This rare genetic condition seems benign, with no discernable disease or functional abnormality noted in follow-up over a 6-mo period.