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














  • 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

  • A splicing mutation in RB1 in low penetrance retinoblastoma.

    abstract::The pediatric eye-tumor retinoblastoma is widely held as a paradigm of human cancer genetics and has been a model system for both the two-hit hypothesis of dominantly inherited cancer as well as for the concept of tumor-specific loss of constitutional heterozygosity to achieve expression of the tumorigenic phenotype. ...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Schubert EL,Strong LC,Hansen MF

    更新日期:1997-10-01 00:00:00

  • Genome-wide study of familial juvenile hyperuricaemic (gouty) nephropathy (FJHN) indicates a new locus, FJHN3, linked to chromosome 2p22.1-p21.

    abstract::Familial juvenile hyperuricaemic (gouty) nephropathy (FJHN), is an autosomal dominant disease associated with a reduced fractional excretion of urate, and progressive renal failure. FJHN is genetically heterogeneous and due to mutations of three genes: uromodulin (UMOD), renin (REN) and hepatocyte nuclear factor-1beta...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Piret SE,Danoy P,Dahan K,Reed AA,Pryce K,Wong W,Torres RJ,Puig JG,Müller T,Kotanko P,Lhotta K,Devuyst O,Brown MA,Thakker RV

    更新日期:2011-01-01 00:00:00

  • Evidence for chromosome instability in vivo in Bloom syndrome: increased numbers of micronuclei in exfoliated cells.

    abstract::The incidence of exfoliated epithelial cells containing micronuclei was determined in two small human populations, one homozygous and the other heterozygous for the Bloom syndrome gene (bl). The objectives of the study were two: to learn whether the chromosome instability featured so prominently by Bloom syndrome (BS)...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Rosin MP,German J

    更新日期:1985-01-01 00:00:00

  • Incidence of seizures and EEG abnormalities among offspring of epileptic patients.

    abstract::The marriage rate of epileptic patients was 62% in males and 78% in females. Compared with the rates in the general population, the male patients had a 15% lower rate, but there was no difference in females. There were 263 patients with at least one offspring selected for the study. There were 234 sons and 272 daughte...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Tsuboi T,Endo S

    更新日期:1977-04-15 00:00:00

  • EagI and NotI linking clones from human chromosomes 11 and Xp.

    abstract::EagI and NotI linking libraries were prepared in the lambda vector, EMBL5, from the mouse-human somatic cell hybrid 1W1LA4.9, which contains human chromosomes 11 and Xp as the only human component. Individual clones containing human DNA were isolated by their ability to hybridise with total human DNA and digested with...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Pook MA,Thakrar R,Pottinger B,Harding B,Porteous D,van Heyningen V,Cowell J,Jones C,Povey S,Davies KE,Thakker RV

    更新日期:1996-06-01 00:00:00

  • Organization and genomic distribution of "82H" alpha satellite DNA. Evidence for a low-copy or single-copy alphoid domain located on human chromosome 14.

    abstract::We have investigated the organization and genomic distribution of sequences homologous to p82H, a cloned human alpha satellite sequence purported, based on previous in situ hybridization experiments, to exist at the centromere of each human chromosome. We report here that, using Southern blotting analysis under condit...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Waye JS,Mitchell AR,Willard HF

    更新日期:1988-01-01 00:00:00

  • Pathologic and nonpathologic variants of the spectrin molecule in two black families with hereditary elliptocytosis.

    abstract::Five patients with hereditary elliptocytosis (HE) from two unrelated black families were studied. The patients had prominent elliptocytosis and a decreased erythrocyte resistance to heat treatment. In one infant blood smears showed elliptocytosis and poikilocytosis; his erythrocytes fagmented at a lower temperature th...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Lecomte MC,Dhermy D,Garbarz M,Feo C,Gautero H,Bournier O,Picat C,Chaveroche I,Ester A,Galand C

    更新日期:1985-01-01 00:00:00

  • Molecular characterisation of two alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) Null(Newport) (Gly115----Ser) and (Pi) Z Wrexham (Ser-19----Leu).

    abstract::Two single point mutations in the alpha-1-antitrypsin gene, resulting in AAT deficiency, have been characterised in heterozygotes by DNA amplification and direct sequencing. The mutations result in amino acid substitutions, Gly115----Ser and Ser-19----Leu, in the leader sequence, respectively, and have been designated...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Graham A,Kalsheker NA,Bamforth FJ,Newton CR,Markham AF

    更新日期:1990-10-01 00:00:00

  • SNURF-SNRPN and UBE3A transcript levels in patients with Angelman syndrome.

    abstract::The imprinted domain on human chromosome 15 consists of two oppositely imprinted gene clusters, which are under the control of an imprinting center (IC). The paternally expressed SNURF-SNRPN gene hosts several snoRNA genes and overlaps the UBE3A gene, which is encoded on the opposite strand, expressed - at least in br...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Runte M,Kroisel PM,Gillessen-Kaesbach G,Varon R,Horn D,Cohen MY,Wagstaff J,Horsthemke B,Buiting K

    更新日期:2004-05-01 00:00:00

  • Nucleolar structures in chromosome and SC preparations from human oocytes at first meiotic prophase.

    abstract::We describe a comparative study of the behavior of nucleolar structures and their relationship with nucleolar chromosomes and synaptonemal complexes at first meiotic prophase of human oocytes in an attempt to elucidate the nature of this cellular organization and to learn more about maternal nondisjunction. The number...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: García M,Dietrich A,Pujol R,Egozcue J

    更新日期:1989-05-01 00:00:00

  • Regional localization of the human factor IX gene by molecular hybridization.

    abstract::A cloned cDNA probe encoding human factor IX was used for detecting homologous sequences in rodent human X chromosome hybrids and in human metaphase chromosome preparations. The results of these studies indicate that human factor IX is localized to the Xq27 leads to Xqter region. ...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Chance PF,Dyer KA,Kurachi K,Yoshitake S,Ropers HH,Wieacker P,Gartler SM

    更新日期:1983-01-01 00:00:00

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

    abstract::The extent of linkage equilibrium was estimated among four recently characterized human fibrinogen restriction fragment length polymorphisms (RFLPs) using a randomly selected group of 110 individuals from California. Two coding region RFLPs, RsaI and MnlI (FGA codon 312 and FGB codon 448, respectively), and two RFLPs ...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Baumann RE,Henschen AH

    更新日期:1994-08-01 00:00:00

  • Ala45Thr polymorphism of the NEUROD1 gene and diabetes susceptibility: a meta-analysis.

    abstract::A meta-analysis assessed whether the Ala45Thr polymorphism of the neurogenic differentiation 1 (NEUROD1) gene is associated with increased risk of diabetes mellitus type 1 (T1D) or type 2 (T2D). Fourteen case-control studies were analyzed, including genotype data on 3,057 patients with diabetes (T1D n=1,213, T2D n=1,8...

    journal_title:Human genetics

    pub_type: 杂志文章,meta分析


    authors: Kavvoura FK,Ioannidis JP

    更新日期:2005-02-01 00:00:00

  • The mutational demography of protein C deficiency.

    abstract::The geographical distribution and prevalence of 256 single base-pair substitutions (105 of them being different) within the coding region of the human protein C (PROC) gene were correlated with their initial likelihoods of generation. A significant positive correlation was observed between these "mutational likelihood...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Krawczak M,Reitsma PH,Cooper DN

    更新日期:1995-08-01 00:00:00

  • Epimutation of the TNDM locus and the Beckwith-Wiedemann syndrome centromeric locus in individuals with transient neonatal diabetes mellitus.

    abstract::Transient neonatal diabetes mellitus (TNDM) is characterised by intra-uterine growth retardation, while Beckwith-Wiedemann syndrome (BWS) is a clinically heterogeneous overgrowth syndrome. Both TNDM and BWS may be caused by aberrant loss of methylation (LOM) at imprinted loci on chromosomes 6q24 and 11p15.5 respective...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Mackay DJ,Hahnemann JM,Boonen SE,Poerksen S,Bunyan DJ,White HE,Durston VJ,Thomas NS,Robinson DO,Shield JP,Clayton-Smith J,Temple IK

    更新日期:2006-03-01 00:00:00

  • DNA-polymorphic patterns linked to the beta-globin genes in German families affected with hemoglobinopathies and thalassemias: a comparison to other ethnic groups.

    abstract::DNA haplotype constellations of the beta-globin gene cluster have been analyzed in German families with hemoglobinopathies (Hb Freiburg, Hb Köln, Hb Presbyterian) and beta-thalassemias. The polymorphic patterns obtained were compared to those found in families from Greece, Italy, and Turkey affected by beta-thalassemi...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Oehme R,Kohne E,Horst J

    更新日期:1985-01-01 00:00:00

  • Two novel mutations in the aquaporin-2 and the vasopressin V2 receptor genes in patients with congenital nephrogenic diabetes insipidus.

    abstract::The vasopressin V2 receptor (V2R) and the aquaporin-2 genes of two unrelated male patients with congenital nephrogenic diabetes insipidus were analyzed. The V2R gene of the patient of family 1 had the wild-type sequence. Consequently, the coding region of the aquaporin-2 gene including the exon-intron junctions was se...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Oksche A,Möller A,Dickson J,Rosendahl W,Rascher W,Bichet DG,Rosenthal W

    更新日期:1996-11-01 00:00:00

  • Disruption of long-range gene regulation in human genetic disease: a kaleidoscope of general principles, diverse mechanisms and unique phenotypic consequences.

    abstract::The precise control of gene expression programs is crucial for the establishment of the diverse gene activity patterns required for the correct development, patterning and differentiation of the myriad of cell types within an organism. The crucial importance of non-coding regions of the genome in the control of gene r...

    journal_title:Human genetics

    pub_type: 杂志文章,评审


    authors: Bhatia S,Kleinjan DA

    更新日期:2014-07-01 00:00:00

  • Molecular analysis of chromosome region 11p13 in patients with Drash syndrome.

    abstract::The association of nephropathy, Wilms' tumour and genital abnormalities is known as Drash syndrome. Two of these features are also seen in the WAGR (Wilms' tumour, aniridia, genito-urinary abnormalities, mental retardation) complex, known to be associated with deletions of chromosome region 11p13. We have carried out ...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Jadresic L,Wadey RB,Buckle B,Barratt TM,Mitchell CD,Cowell JK

    更新日期:1991-03-01 00:00:00

  • HLA-A, B, C, DR alleles in congenital adrenal hyperplasia.

    abstract::HLA markers (A, B, C, DR loci) were determined for the members of 52 unrelated families with at least one child suffering from congenital adrenal hyperplasia due to 21 hydroxylase deficiency, permitting genotyping. The gene frequencies of the 52 index cases were compared with those obtained from the patients' normal h...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Couillin P,Kottler-Missonnier ML,Grisard MC,Hors J,Feingold J,Boué J,Boué A

    更新日期:1980-01-01 00:00:00

  • Investigations on the polymorphism of glyoxalase I (EC in the population of Hessen, Germany.

    abstract::The phenotypes of glyoxalase I (GLO) were determined in a random population from Hessen (Germany) by high-voltage agarose gel electrophoresis. The gene frequencies in 1150 unrelated individuals were 0.4391 for GLO1 and 0.5609 fro GLO2. Rare phenotypes were not observed. The segregation of phenotypes in 50 families an...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Kühnl P,Schwabenland R,Spielmann W

    更新日期:1977-08-31 00:00:00

  • Trisomy 7 in non-neoplastic tubular epithelial cells of the kidney.

    abstract::The cellular origin of trisomy 7 in non-neoplastic kidney tissue specimens from 10 patients, seven with malignant tumors and three with non-neoplastic kidney diseases, was studied by the MAC (morphology antibody chromosomes) technique, which allows analysis of cellular morphology/histology, immunophenotype, and chromo...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Knuutila S,Larramendy ML,Elfving P,el-Rifai W,Miettinen A,Mitelman F

    更新日期:1995-02-01 00:00:00

  • Linkage analysis identifies the thyroglobulin gene region as a major locus for familial congenital hypothyroidism.

    abstract::Congenital hypothyroidism affects 1/3000-4000 newborns and it has been estimated that 10-20% are familial cases with an autosomal recessive mode of inheritance. Previous studies of mostly individual cases have led to the identification of mutations in a number of genes, indicating that it is a genetically heterogeneou...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Ahlbom BE,Yaqoob M,Gustavsson P,Abbas HG,Annerén G,Larsson A,Wadelius C

    更新日期:2002-02-01 00:00:00

  • Combined action of isoniazid and para-aminosalicylic acid in vivo on human chromosomes in lymphocyte cultures.

    abstract::Two antitubercular drugs, viz., isoniazid (INH) and para-aminosalicylic acid (PAS), in combination, were evaluated for their in vivo clastogenic effects of human lymphocyte chromosomes. Lymphocyte cultures from tuberculosis patients taking a therapeutic dose of INH and PAS for a period of not less than 3 months and fr...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Jaju M,Jaju M,Ahuja YR

    更新日期:1981-01-01 00:00:00

  • Hereditary hemolytic anemia with erythrocyte phosphofructokinase deficiency: studies of some properties of erythrocyte and muscle enzyme.

    abstract::A case of hereditary nonspherocytic hemolytic anemia associated with partial erythrocyte PFK deficiency without muscular symptoms is reported: erythrocyte enzyme activity in the propositus was 60% of normal. Kinetic studies of erythrocyte PFK revealed increased sensitivity to ATP inhibition and decreased sensitivity t...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Etiemble J,Kahn A,Boivin P,Bernard JF,Goudemand M

    更新日期:1976-01-28 00:00:00

  • New polymorphisms and markers in the HLA class I region: relevance to hereditary hemochromatosis (HFE).

    abstract::Hereditary hemochromatosis (HFE) is an inherited disorder whose gene lies in the proximity of the histocompatibility antigen (HLA) class I region, on 6p21.3. Despite efforts in refining the HFE region, a number of informative DNA markers, linked to the disease locus and amenable to use in an assay based on the polymer...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Totaro A,Grifa A,Roetto A,Lunardi C,D'Agruma L,Sbaiz L,Zelante L,De Sandre G,Camaschella C,Gasparini P

    更新日期:1995-04-01 00:00:00

  • Interaction between obesity and genetic polymorphisms in the apolipoprotein CIII gene and lipoprotein lipase gene on the risk of hypertriglyceridemia in Chinese.

    abstract::To understand the effects of the interaction between genetic polymorphisms and obesity on the risk of hypertriglyceridemia (HTG), two polymorphisms, an SstI polymorphism on the apolipoprotein CIII gene and a HindIII polymorphism on the lipoprotein lipase gene, were analyzed in 339 Chinese subjects with (82 cases in th...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Ko YL,Ko YS,Wu SM,Teng MS,Chen FR,Hsu TS,Chiang CW,Lee YS

    更新日期:1997-09-01 00:00:00

  • Characterization of mutants of the vitamin D-binding protein/group-specific component: molecular evolution of GC*1A2 and GC*1A3, common in some Asian populations.

    abstract::A well defined polymorphism of vitamin D-binding/group-specific component (GC) residues in exon 11. To characterize the molecular basis of GC*1A2 and GC*1A3, common in some Asian populations, we analyzed all coding exons amplified by the polymerase chain reaction. GC*1F was divided into GC*1FC and GC*1FT by a C-T tran...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Yuasa I,Kofler A,Braun A,Umetsu K,Bichlmaier R,Kammerer S,Cleve H

    更新日期:1995-05-01 00:00:00

  • Bi-allelic BRWD1 variants cause male infertility with asthenoteratozoospermia and likely primary ciliary dyskinesia.

    abstract::Genetics-associated asthenoteratozoospermia is often seen in patients with multiple morphological abnormalities of the sperm flagella (MMAF). Although 24 causative genes have been identified, these explain only approximately half of patients with MMAF. Since sperm flagella and motile cilia (especially respiratory cili...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Guo T,Tu CF,Yang DH,Ding SZ,Lei C,Wang RC,Liu L,Kang X,Shen XQ,Yang YF,Tan ZP,Tan YQ,Luo H

    更新日期:2021-01-03 00:00:00