Incomplete penetrance in primary immunodeficiency: a skeleton in the closet.


:Primary immunodeficiencies (PIDs) comprise a diverse group of over 400 genetic disorders that result in clinically apparent immune dysfunction. Although PIDs are classically considered as Mendelian disorders with complete penetrance, we now understand that absent or partial clinical disease is often noted in individuals harboring disease-causing genotypes. Despite the frequency of incomplete penetrance in PID, no conceptual framework exists to categorize and explain these occurrences. Here, by reviewing decades of reports on incomplete penetrance in PID we identify four recurrent themes of incomplete penetrance, namely genotype quality, (epi)genetic modification, environmental influence, and mosaicism. For each of these principles, we review what is known, underscore what remains unknown, and propose future experimental approaches to fill the gaps in our understanding. Although the content herein relates specifically to inborn errors of immunity, the concepts are generalizable across genetic diseases.


Hum Genet


Human genetics


Gruber C,Bogunovic D




Has Abstract


2020-06-01 00:00:00














  • Beta-globin gene linked DNA haplotypes and frameworks in three South-East Asian populations.

    abstract::DNA haplotypes and frameworks (numbers in parenthesis) linked to the beta-globin gene were determined by restriction fragment analysis using eight restriction endonucleases on 86 (97) chromosomes bearing the normal beta-globin gene (HBB*A) and 108 (118) chromosomes bearing HBB*E in subjects homozygous for HBB*A or HBB...

    journal_title:Human genetics

    pub_type: 杂志文章


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    更新日期:1988-09-01 00:00:00

  • A case of trisomy for the short arm of chromosome no. 9(+9(p)).

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    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Käosaar ME,Mikelsaar AV,Talvik TA,Mikelsaar RV

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  • Malate dehydrogenase types in the Asian-Pacific area, and a description of new phenotypes.

    abstract::A survey of more than 21 000 haemolysates from blood samples collected in various parts of south and southeast Asia, Australasia and the Western Pacific and examined in this laboratory has revealed several new alleles controlling variants of sMDH; in addition, further information has been provided on the distribution ...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Blake NM

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  • Microdeletion 22q11 in complex cardiovascular malformations.

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    journal_title:Human genetics

    pub_type: 杂志文章


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  • Is there a correlation between morphological and cytogenetic findings in placental tissue from early missed abortions?

    abstract::A retrospective study of 200 missed abortions was performed to determine whether morphological criteria alone are sufficient to ascertain a chromosomal aetiology. Placental changes were classified into five morphological and four morphometric groups, according to the severity of alterations, and were then correlated w...

    journal_title:Human genetics

    pub_type: 杂志文章


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    journal_title:Human genetics

    pub_type: 杂志文章


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    更新日期:1996-02-01 00:00:00

  • Cytologic demonstration of differential activity of rRNA gene clusters in different human tissues.

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    journal_title:Human genetics

    pub_type: 杂志文章


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    journal_title:Human genetics

    pub_type: 杂志文章


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  • Linkage disequilibrium relationships among four polymorphisms within the human fibrinogen gene cluster.

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    journal_title:Human genetics

    pub_type: 杂志文章


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    journal_title:Human genetics

    pub_type: 杂志文章


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    journal_title:Human genetics

    pub_type: 杂志文章,评审


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    更新日期:2014-10-01 00:00:00

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    journal_title:Human genetics

    pub_type: 杂志文章


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    journal_title:Human genetics

    pub_type: 杂志文章


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    journal_title:Human genetics

    pub_type: 杂志文章


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    journal_title:Human genetics

    pub_type: 杂志文章


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    journal_title:Human genetics

    pub_type: 杂志文章,多中心研究


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    journal_title:Human genetics

    pub_type: 杂志文章


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    journal_title:Human genetics

    pub_type: 杂志文章


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    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Voullaire LE,Webb GC,Leversha MA

    更新日期:1987-06-01 00:00:00

  • SONIC HEDGEHOG mutations causing human holoprosencephaly impair neural patterning activity.

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    journal_title:Human genetics

    pub_type: 杂志文章


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    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Qazi QH,Madahar C,Yuceoglu AM

    更新日期:1980-02-01 00:00:00

  • Fine-mapping the genetic basis of CRP regulation in African Americans: a Bayesian approach.

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    journal_title:Human genetics

    pub_type: 杂志文章


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    更新日期:2008-07-01 00:00:00

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    journal_title:Human genetics

    pub_type: 杂志文章


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    更新日期:1995-07-01 00:00:00

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    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Dallapiccola B,Porfirio B,Mokini V,Alimena G,Isacchi G,Gandini E

    更新日期:1985-01-01 00:00:00

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    abstract::Nitric oxide (NO) mediates host resistance to severe malaria and other infectious diseases. NO production and mononuclear cell expression of the NO producing enzyme-inducible nitric oxide synthase (NOS2) have been associated with protection from severe falciparum malaria. The purpose of this study was to identify sing...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Levesque MC,Hobbs MR,O'Loughlin CW,Chancellor JA,Chen Y,Tkachuk AN,Booth J,Patch KB,Allgood S,Pole AR,Fernandez CA,Mwaikambo ED,Mutabingwa TK,Fried M,Sorensen B,Duffy PE,Granger DL,Anstey NM,Weinberg JB

    更新日期:2010-02-01 00:00:00

  • Extended polymorphism of the human esterase D isozyme system: description of a "new" allele EsD*11.

    abstract::Using "new" techniques (malic acid thin layer agarose gel electrophoresis and/or isoelectric focusing), the polymorphism of the human red cell isozyme system esterase D (ESD) was shown to be extended. We report the gene frequencies observed among 312 unrelated Caucasian individuals living in the Düsseldorf area. The f...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Henke J,Schweitzer H,Bär W,Weidinger S,Weissmann J,Baur MP

    更新日期:1986-05-01 00:00:00

  • Reciprocal translocation t(5;6)(p13;q27) through three generations: case report of cri du chat syndrome.

    abstract::A male infant with cri du chat syndrome was found to have a deletion of the short arm of No. 5 chromosome and which was due to maternal reciprocal translocation t(5;6)(p13;q27). His elder sister and his grandfather were also identified as the translocation carriers. ...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Hashimoto T,Tsukino R,Chiyo H,Furuyama J

    更新日期:1980-02-01 00:00:00

  • A myeloblastin/proteinase-3 cDNA clone identifies a BglII and a PvuII restriction fragment length polymorphism.

    abstract::A myeloblastin/proteinase-3 (MBN/PR-3) cDNA probe detects two bi-allelic (BglII, PvuII) DNA polymorphisms. These restriction fragment length polymorphisms provide new genetic markers on chromosome 19. ...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Schwaller J,Chen T,Fey MF,Tobler A

    更新日期:1993-11-01 00:00:00

  • Molecular characterisation of the pericentric inversion that distinguishes human chromosome 5 from the homologous chimpanzee chromosome.

    abstract::Human and chimpanzee karyotypes differ by virtue of nine pericentric inversions that serve to distinguish human chromosomes 1, 4, 5, 9, 12, 15, 16, 17, and 18 from their chimpanzee orthologues. In this study, we have analysed the breakpoints of the pericentric inversion characteristic of chimpanzee chromosome 4, the h...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Szamalek JM,Goidts V,Chuzhanova N,Hameister H,Cooper DN,Kehrer-Sawatzki H

    更新日期:2005-07-01 00:00:00

  • Identification of genetic associations of SP110/MYBBP1A/RELA with pulmonary tuberculosis in the Chinese Han population.

    abstract::Genetic factors play important roles in the development of tuberculosis (TB). SP110 is a promising candidate target for controlling TB infections. However, several studies associating SP110 single nucleotide polymorphisms (SNPs) with TB have yielded conflicting results. This may be partly resolved by studying other ge...

    journal_title:Human genetics

    pub_type: 杂志文章,meta分析


    authors: Cai L,Deng SL,Liang L,Pan H,Zhou J,Wang MY,Yue J,Wan CL,He G,He L

    更新日期:2013-03-01 00:00:00