Alpha‐1‐antitrypsin‐deficient phenotype is not maintained by segregation distortion

Suarez, Brian K.; Pierce, John A.

doi:10.1002/ajpa.1330620105

Cited by 3 publications

(1 citation statement)

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“…But this is not significant and might merely reflect the small size of the sample. However it has previously been suggested that there might be disturbances of the segregation ratio in families with the Z allele and this topic is still the subject of debate (Cook, 1974;Fagerhol and Cox, 1981 ;Suarez and Pierce, 1983).…”

Section: Discussionmentioning

confidence: 99%

Prenatal diagnosis of alpha‐1‐antitrypsin deficiency by fetal blood sampling

et al. 1987

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Fetal blood sampling for the diagnosis of alpha-1-antitrypsin deficiency using protein isoelectric focusing was carried out in the period 1980-1985. The results of 25 cases from 18 mothers are reported. All had a previous history of a PiZ child affected by liver disease. The method was found to be technically satisfactory and the fetal results were subsequently confirmed in all 18 cases where follow-up was possible. The fetus was found to be PiZ in nine cases and all these pregnancies were terminated. Of the remaining pregnancies three cases aborted or were delivered prematurely and 13 proceeded to term without complications.

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Section: Discussionmentioning

confidence: 99%

Prenatal diagnosis of alpha‐1‐antitrypsin deficiency by fetal blood sampling

et al. 1987

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Testicular Function and Fertility in Men with Homozygous Alpha-1 Antitrypsin Deficiency

et al. 2009

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Fertility and testicular function were studied in eight men with severe homozygous (Pi ZZ variant genotype) alpha-I antitrypsin (AAT) deficiency. Age-and marital duration standardized fertility, clinical androgenic features, mean testicular volume, plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and semen analysis were all normal apart from a reduction in semen volume. Mean plasma total and free testosterone were elevated and the percentage free testosterone reduced compared with age-matched, healthy fertile controls indicative of increased sex-hormone binding globulin (SHBG) levels representing an early marker for subclinical hepatic dysfunction associated with AATdeficiency. In view of the preservation of normal fertility and testicular function despite chronic respiratory disease and premature death with deleterious AAT gene variants, it is proposed that the high prevalence of genetic polymorphism in the AAT protein may be maintained by the chronological assynchrony of the periods of maximal male reproductive activity (40 years) and the late onset (> 40 years) of symptoms in severe AAT deficiency rather than by any balance between reduced reproductive fitness of homozygotes and heterozygote advantage. Hodenfunktion und Fertilitat bei Mannern mit homozygotem Alpha-I -Antitrypsin-MangelZusammenfassung: Fertilitiit und Hodenfunktion wurden bei 8 Mginnem mit schwerem homozygoten (Pi ZZ Genotypvariante) Alpha-1-Antitrypin (AAT)-Mange1 untemcht . Die nach Alter und Ehedauer standardisierte Fertilitiit, die klinischen androgenen Merkmale, Durchschnittshodenvolumen, durchschnittlicher Plasma-LH und -FSH-Spiegel sowie die Samenuntemchung waren Gmtlich normal mit Ausnahme eines verminderten Ejakulatvolumens. Das mittlere Gesamt-Testosteron und das freie Testosteron im Plasma waren im Vergleich zu altersgleichen gesunden und fertilen Kontrollpersonen erhoht, der Prozentsatz des freien Testosteron vennindert. Dieses weist ein erhohtes androgenbindendes Globulin (SHBG) als einen friihen Anzeiger fur subklinische Leberfehlfunktion im Zusammenhang mit dem AAT-Mange1 hin. In Hinsicht auf die normale Fertilitiit und Hodenfunktion trotz chronischer Lungenkrankheit und vorzeitigem Tod bei deletiiren AATGenvarianten w i d angenommen, dal3 die Erhaltung der hohen Priivalenz des genetischen Polymorphismus des AATProteins durch die chronologische Asynchronie der Zeitrtiume der maximalen mannlichen Reproduktionsaktivitiit (unter 40 Jahre) und dem des spateren Key words: Alpha-1 antitrypsin, testismale fertility, chronic respiratory diseasesex-hormone binding globulinfertility, antitrypsinandrologia 18 (1986)

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Heterozygosity of α₁-Antitrypsin: A Health Risk?

Feld

1989

Critical Reviews in Clinical Laboratory Sciences

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alpha 1-Antitrypsin is a serum glycoprotein synthesized in the liver. It consists of a single polypeptide chain with a molecular weight of about 52,000. The molecule exhibits great genetic diversity with multiple codominant alleles at a single autosomal locus. The majority of the population expresses the M allele. The Z allele, which is the result of a single amino acid substitution, results in levels of alpha 1-antitrypsin that are only 10 to 15% of normal when inherited in the homozygous state. Two main pathological consequences of this state are liver and lung disease. The homozygous S phenotype has also been associated with reduced alpha 1-antitrypsin levels and pathology. The homozygous Z phenotype has an incidence of about 1 in 1700 in certain European populations. People who are heterozygous for the S or Z allele usually have alpha 1-antitrypsin levels which are about 60% of normal. The combined frequency of these alleles in the population may reach 10 to 15%. This review examines the controversy as to whether these individuals are at increased risk for pathology due to their reduced alpha 1-antitrypsin levels.

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Alpha‐1‐antitrypsin‐deficient phenotype is not maintained by segregation distortion

Cited by 3 publications

References 32 publications

Prenatal diagnosis of alpha‐1‐antitrypsin deficiency by fetal blood sampling

Prenatal diagnosis of alpha‐1‐antitrypsin deficiency by fetal blood sampling

Testicular Function and Fertility in Men with Homozygous Alpha-1 Antitrypsin Deficiency

Heterozygosity of α₁-Antitrypsin: A Health Risk?

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Alpha‐1‐antitrypsin‐deficient phenotype is not maintained by segregation distortion

Cited by 3 publications

References 32 publications

Prenatal diagnosis of alpha‐1‐antitrypsin deficiency by fetal blood sampling

Prenatal diagnosis of alpha‐1‐antitrypsin deficiency by fetal blood sampling

Testicular Function and Fertility in Men with Homozygous Alpha-1 Antitrypsin Deficiency

Heterozygosity of α1-Antitrypsin: A Health Risk?

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Heterozygosity of α₁-Antitrypsin: A Health Risk?