Identical 3250-bp deletion between two AluI repeats in the ADA genes of unrelated ADA−SCID patients

Berkvens, Th.M.; Ormondt, H. van; Gerritsen, E. J. A.; Khan, P. Meera; Eb, A. J. Van Der

doi:10.1016/0888-7543(90)90190-6

Cited by 28 publications

(8 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both de novo and inherited CNVs are recognized in many human conditions[23; 24; 25; 26]. Low copy number repeats flank the DiGeorge syndrome region at 22q11.2[27] and Alu-mediated deletions have resulted in Bruton’s agammaaglobulinemia[16; 28; 29; 30] and ADA deficiency[31; 32]. CNV at 16p11.2 has been estimated to occur in 1.5% of subjects with developmental delay, 1% of individuals with autism, and 0.1% in patients with psychiatric or language disorders, but less than 0.01% in the general population[18].…”

Section: Discussionmentioning

confidence: 99%

Severe combined immunodeficiency (SCID) and attention deficit hyperactivity disorder (ADHD) associated with a coronin-1A mutation and a chromosome 16p11.2 deletion

Shiow¹,

Akana²,

Cyster³

et al. 2009

Clinical Immunology

129

108

View full text Add to dashboard Cite

Defects causing severe combined immunodeficiency (SCID) have been reported in pathways mediating antigen receptor rearrangement, antigen receptor and cytokine signaling, and purine metabolism. Recognizing that the actin regulator Coronin-1A is essential for development of a normal peripheral T cell compartment in mouse models, we identified absence of Coronin-1A in a girl with T-B+NK+ SCID who suffered recurrent infections including severe post-vaccination varicella at age 13 months. Murine Coronin-1A is essential for release of T cells from the thymus, consistent with the paradoxically detectable thymus in our patient. Molecular analysis revealed a 2 bp deletion in the paternal CORO1A coding sequence paired with a 600kb de novo deletion encompassing CORO1A on the maternal allele. This genomic region at 16p11.2 is subject to recurrent copy number variations associated with autism spectrum disorders, including attention deficit and hyperactivity, present in our patient. This case highlights the first link between actin cytoskeleton regulation and SCID.

show abstract

Section: Discussionmentioning

confidence: 99%

Severe combined immunodeficiency (SCID) and attention deficit hyperactivity disorder (ADHD) associated with a coronin-1A mutation and a chromosome 16p11.2 deletion

Shiow¹,

Akana²,

Cyster³

et al. 2009

Clinical Immunology

129

108

View full text Add to dashboard Cite

show abstract

“…Indeed, Alu sequences flanking deletion breakpoints have been noted in a considerable number of human genetic conditions involving defects in the genes for a-globin (Nicholls et al 1987), [3-globin (Henthorn et al 1986), growth hormone (Vnencak-Jones et al 1988), apolipoprotein B (Huang et al 1989, [3-hexosaminidase (Myerowitz and Hogikyan 1987), adenosine deaminase (Markert et al 1988;Berkvens et al 1990), a-galactosidase A (Kornreich et al 1990), C1 inhibitor (Stoppa-Lyonnet et al 1990 and LDL receptor (Hobbs et al 1986;Lehrman et al 1985Lehrman et al , 1986Lehrman et al , 1987. Deletion is proposed to occur by meiotic (or mitotic) recombination between chromosomes misaligned at these partially homologous sequences.…”

Section: Introductionmentioning

confidence: 99%

Gene deletions causing human genetic disease: mechanisms of mutagenesis and the role of the local DNA sequence environment

1991

View full text Add to dashboard Cite

Reports describing short (less than 20 bp) gene deletions causing human genetic disease were collated in order to study underlying causative mechanisms. Deletion breakpoint junction regions were found to be non-random both at the nucleotide and dinucleotide sequence levels, an observation consistent with an endogenous sequence-directed mechanism of mutagenesis. Direct repeats of between 2bp and 8bp were found in the immediate vicinity of all but one of the 60 deletions analysed. Direct repeats are a feature of a number of recombination, replication or repair-based models of deletion mutagenesis and the possible contribution of each to the spectrum of mutations examined was assessed. The influence of parameters such as repeat length and length of DNA between repeats was studied in relation to the frequency, location and extent of these deletions. Findings were broadly consistent with a slipped mispairing model but the predicted deletion of one whole repeat copy was found only rarely. A modified version of the slipped mispairing hypothesis was therefore proposed and was shown to possess considerable explanatory value for approximately 25% of deletions examined. Whereas the frequency of inverted repeats in the vicinity of gene deletions was not significantly elevated, these elements may nevertheless promote instability by facilitating the formation of secondary structure intermediates. A significant excess of symmetrical sequence elements was however found at sites of single base deletions. A new model to explain the involvement of symmetric elements in frameshift mutagenesis was devised, which successfully accounted for a majority of the single base deletions examined. In general, the loss of one or a few base pairs of DNA was found to be more compatible with a replication-based model of mutagenesis than with a recombination or repair hypothesis. Seven hitherto unrecognized hotspots for deletion were noted in five genes (AT3, F8, HBA, HBB and HPRT). Considerable sequence homology was found between these different sites, and a consensus sequence (TGA/GA/GG/TA/C) was drawn up. Sequences fitting this consensus (i) were noted in the immediate vicinity of 41% of the other (sporadic) gene deletions, (ii) were found frequently at sites of spontaneous deletion in the hamster APRT gene, (iii) were found to be associated with many larger human gene deletions/translocations, (iv) act as arrest sites for human polymerase alpha during DNA replication and (v) have been shown by in vitro studies of human polymerase alpha to be especially prone to frameshift mutation.(ABSTRACT TRUNCATED AT 400 WORDS)

show abstract

“…In the LDL receptor gene, four deletions and one duplication involve Alu sequences (9 of 10 junctions) (Lehrman et al, 1987). Homologous recombination between Alu sequences, typically at regions of 20-40 bp of perfect homology, have also been described in the adenosine deaminase, C1 inhibitor, and a-globin genes (Berkvens et al, 1990;Ariga et al, 1990;Nicholls et al, 1987).…”

Section: Deletion Patterns In Other Genesmentioning

confidence: 99%

Deletions with inversions: Report of a mutation and review of the literature

et al. 1993

View full text Add to dashboard Cite

show abstract

Identical 3250-bp deletion between two AluI repeats in the ADA genes of unrelated ADA−SCID patients

Cited by 28 publications

References 19 publications

Severe combined immunodeficiency (SCID) and attention deficit hyperactivity disorder (ADHD) associated with a coronin-1A mutation and a chromosome 16p11.2 deletion

Severe combined immunodeficiency (SCID) and attention deficit hyperactivity disorder (ADHD) associated with a coronin-1A mutation and a chromosome 16p11.2 deletion

Gene deletions causing human genetic disease: mechanisms of mutagenesis and the role of the local DNA sequence environment

Deletions with inversions: Report of a mutation and review of the literature

Contact Info

Product

Resources

About