Prenatal Detection of epidermolysis bullosa letalis with pyloric atresia in a fetus by abnormal ultrasound and elevated alpha‐fetoprotein

Dolan, Cynthia R.; Smith, Lynne T.; Sybert, Virginia P.

doi:10.1002/ajmg.1320470320

Cited by 35 publications

(24 citation statements)

References 37 publications

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“…The synthesis of AFP has further been reported in neonatal rat skin implants (Mujoo et al, 1983), but has yet to be confirmed. The elevated AFP levels reported in infants with functional and dystrophic epidermolysis bullosa, aplasia cutis congenita, and epidermolysis bullosa letalis (Dolan et al, 1993;Drugan et al, 1995;Gerber et al, 1995) attest to a possible linkage between AFP and skin intermediate filaments. In fact, it has been suggested that AFP screening would obviate the need for fetal skin sampling in the prenatal diagnosis of these disorders (Gerber et al, 1995).…”

Section: J) Amino Acid-rich Repeat Sitesmentioning

confidence: 87%

Mapping of Structure-Function Peptide Sites on the Human Alpha-fetoprotein Amino Acid Sequence

Mizejewski¹

2011

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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The structure of alpha-fetoprotein (AFP) is presen-ted in light of AFP membership and position in the albuminoid gene family in comparison to other gene family members. Ontogenetic AFP gene expression is reviewed considering AFP mRNA presence in various tissues at different times during development. The multiple molecular variant forms of AFP are discussed in relation to published reports of AFP binding proteins and cell surface receptors. The atlas further shows AFP as a protein consisting of multiple peptide-cassettes consisting of amino acid (AA) sequence stretches matched to peptide segments on prohormones and biological response modifier proteins. Such AFP peptide segments could potentially serve as delivery agents which could target vascular, neuroendocrine, or gastrointestinal cells. A discussion follows in which peptide epitopes, extracellular matrix proteins, serine proteases, extracellular matrix, and cellular adhesion AA identity sites on AFP are considered. The AFP molecule is also viewed as a carrier/ transport protein based on AA sequence comparison of various proteins that bind hydropho-bic ligands and heavy metals similar to AFP binding of such components. An analysis of trans-cription factors, tumor suppressors, and AA-rich motifs follows, interfaced with dimerization and nuclear localization sequence matches identified on the AFP molecule. Emphasis is further placed upon homeodomain and apoptosis AA sequence identi-ties given that AFP serves as a fetal, phasespecific protein throughout embryogenesis, histogenesis, and organogenesis. AFP AA sequences are further presented as peptide identification sites for Mapping of Structure-Function Peptide Sites on the Human Alpha-fetoprotein Amino Acid SequenceMizejewski GJ Atlas Genet Cytogenet Oncol Haematol. 2010; 14(2) 170 growth factors, receptors, cytoskeletal proteins, and chemo-kines. A closing discussion summarizes the multi-ple and varied motifs of peptide sequences matched to AAs on each of AFP's three domains. This study indicates that short peptide segments, in addition to full-length AFP, and domain and subdomain fragments of AFP, could be employed as functional agents to help unravel the complexity of biological roles ascribed to human AFP.

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Section: J) Amino Acid-rich Repeat Sitesmentioning

confidence: 87%

Mapping of Structure-Function Peptide Sites on the Human Alpha-fetoprotein Amino Acid Sequence

Mizejewski¹

2011

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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“…The coexistence of pyloric atresia and junctional epidermolysis bullosa has been repeatedly observed (Korber and Glasson, 1977;Cowton et al, 1982;Achiron et al, 1992;Lestringant et al, 1992;Dolan et al, 1993;Valari et al, 1995;Shaw et al, 1997).…”

Section: Discussionmentioning

confidence: 97%

“…It was even thought that sonographic signs were suggestive of the PA-JEB syndrome. A review of the literature was undertaken and reinforced our conviction that the fetus was affected with PA-JEB (Achiron et al, 1992;Dolan et al, 1993;Weissman et al, 1994). When informed of the extreme severity of the disease, the parents agreed to a fetal skin biopsy which they had at ®rst turned down.…”

Section: Ultrasound Examinationmentioning

confidence: 98%

“…However: (1) Achiron et al (1992), described partially similar ®ndings in a fetus at riskÐthe infant was affected and died at 6 days of age. (2) By ultrasonography, Dolan et al (1993), demonstrated gastric dilatation, echogenic particles in the amniotic¯uid, elevated amniotic uid AFP and positive acetylcholinesterase at 22.5 weeks' gestation.…”

Section: Epidermolysis Bullosamentioning

confidence: 98%

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Prenatal diagnosis of pyloric atresia-junctional epidermolysis bullosa syndrome in a fetus not known to be at risk

et al. 2000

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Junctional epidermolysis bullosa with pyloric atresia (PA-JEB) is a highly lethal, inherited, autosomal recessive disease. Thus far, prenatal diagnosis of this syndrome was only realized on pregnancies at risk for recurrence. We report the case of a 26-year-old woman, first cousin to her husband, who had undergone amniocentesis for polyhydramnios. The karyotype was normal but the amniotic fluid contained acetylcholinesterase. A targeted scan at 25 weeks' gestation did not find spina bifida, but polyhydramnios with a dilated stomach, and several other anomalies: echogenic particles in the amniotic fluid, a thin skin which closely adhered to the nasal bones, narrow nostrils, abnormal ears, fisted hands, malposition of both first toes, and kidney malformation. Despite no previous case in the family, it was thought that sonographic findings were suggestive of the PA-JEB syndrome. A fetal skin biopsy was carried out at 28 weeks' gestation. The ultrastructural examination of fetal skin displayed JEB. Genetic analysis detected a homozygous mutation in the gene encoding integrin alpha 6. Termination of pregnancy was carried out at 29 weeks' gestation. These results illustrate that in the case of a fetus not known to be at risk, diagnosis of PA-JEB can be achieved by ultrasound findings leading to fetal skin biopsy and ultrastructural examination of blistered epidermis. Some new sonographic signs should raise the possibility of significant cutaneous desquamation and blister formation in a fetus, especially when there is positive amniotic acetylcholinesterase coupled with elevated alpha-fetoprotein or suspected pyloric atresia.

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“…The amniotic fluid (AF) of such fetuses contained high levels of acetylcholinesterase (Ache) enzyme, however, the karyotype was normal. Some fetuses further displayed mutated integrin-alpha-6 and B4 genes, kidney malformations, hypoplastic or absent hemi-desmosomes along the dermal-epidermal junction, and aplasia cutis congenital [47,48]. Fetal skin biopsies are usually performed but can produce false positive results unless electron microscopic examination is available.…”

Section: Afp and Inflammation During Pregnancymentioning

confidence: 99%

Alpha-Fetoprotein (AFP) and Inflammation: Is AFP an Acute and/or Chronic Phase Reactant?

2015

J Hematol Thrombo Dis

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Even though alpha-fetoprotein has long been implicated with inflammation during pregnancy and adult liver dysfunction, the literature lacks a review of such a relationship. Clarification of the role of alpha-fetoprotein in the inflammatory response is explored in the present report regarding AFP's participation as a positive and/or negative phase inflammatory reactant. Inflammation follows a complex succession of vascular changes involving alternations in blood and lymphatic vessels both at local intracellular sites and at the organ (liver) level. The inflammatory response may result in either an acute phase or develop into a chronic phase following injury or insult from foreign bodies, microbes, toxins, carcinogens, or autoimmune self-antigens. The site of inflammation attracts pleiomorphic cell infiltrates which secrete various chemical mediators such as cytokines, chemokines, interferons, histamines, and a host of others. It is herein demonstrated that alpha-fetoprotein can serve both as an acute and a chronic phase reactant depending on its stage of ontogeny. It was found that alpha-fetoprotein functions as a positive acute phase reactant in the embryo, fetus, and placenta during pregnancy. In contrast, alpha-fetoprotein proceeds to function as a negative acute phase protein in the postnatal and adult periods of life, especially following liver dysfunction and toxic insult. In chronic viral-induced inflammation of the liver, especially viral hepatitis, alpha-fetoprotein appears to serve as a positive phase inflammatory reactant.

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Prenatal Detection of epidermolysis bullosa letalis with pyloric atresia in a fetus by abnormal ultrasound and elevated alpha‐fetoprotein

Cited by 35 publications

References 37 publications

Mapping of Structure-Function Peptide Sites on the Human Alpha-fetoprotein Amino Acid Sequence

Mapping of Structure-Function Peptide Sites on the Human Alpha-fetoprotein Amino Acid Sequence

Prenatal diagnosis of pyloric atresia-junctional epidermolysis bullosa syndrome in a fetus not known to be at risk

Alpha-Fetoprotein (AFP) and Inflammation: Is AFP an Acute and/or Chronic Phase Reactant?

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