Two new mutations at the adenosine deaminase (ADA) locus (Q254X and del nt1050-54) unusual for not being missense mutations

Hirschhorn, Rochelle; Chen, A. S.; Israni, Ajay K.; Yang, Dongliang; Huie, Maryann L.

doi:10.1002/humu.1380020415

Cited by 14 publications

(8 citation statements)

References 8 publications

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“…This deletion shifts the reading frame and mutates codons 319-321 from EEE to GVX, eliminating the last 43 amino acids. This same 5-bp deletion has recently been found in a patient with early-onset SCID3 and in unrelated ADA-deficient patients (36). MJ lacks a polymorphism, Lys8O > Arg, found in one of these patients, suggesting an independent origin, consistent with the suggestion that the mutation is at a deletional hot spot.…”

Section: Patientssupporting

confidence: 85%

Novel splicing, missense, and deletion mutations in seven adenosine deaminase-deficient patients with late/delayed onset of combined immunodeficiency disease. Contribution of genotype to phenotype.

Santistéban¹,

Arredondo-Vega²,

Kelly³

et al. 1993

J. Clin. Invest.

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Section: Patientssupporting

confidence: 85%

Novel splicing, missense, and deletion mutations in seven adenosine deaminase-deficient patients with late/delayed onset of combined immunodeficiency disease. Contribution of genotype to phenotype.

Santistéban¹,

Arredondo-Vega²,

Kelly³

et al. 1993

J. Clin. Invest.

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“…Our patient developed progressively worsening infections that necessitated HCT, which has been curative. Although the majority of SCID infants are diagnosed in the first year of life, delayed presentations have been described, some of which involve leaky genetic defects, such as hypomorphic mutations allowing residual activity of the ADA enzyme[10; 11]. In contrast, our patient carries null alleles of CORO1A .…”

Section: Discussionmentioning

confidence: 91%

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

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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.

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“…Sequence analysis of the ADA gene in the disease-associated ADA-iPS2 line revealed a compound heterozygote: a GGG to GAA transition mutation at exon 7, causing a G216R amino acid substitution (Figure 1B); the other allele is known to have a frame-shift deletion (-GAAGA) in exon 10 (Hirschhorn et al, 1993). The SBDS-iPS8 line harbors point mutations at the IV2+2T>C intron 2 splice donor site (Figure 1B) and IVS3-1G>A mutation (Austin et al, 2005).…”

Section: Resultsmentioning

confidence: 99%

“…Mutated alleles identical to the original specimens were verified by DNA sequencing. Adenosine deaminase deficiency line ADA-iPS2, a compound heterozygote: GGG to GAA double transition in exon 7 of one allele (G216R substitution); the second allele is an exon 10 frame-shift deletion (-GAAGA) (Hirschhorn et al, 1993). Shwachman-Bodian-Diamond syndrome line SBDS-iPS8 is also a compound heterozygote: point mutations at the IV2+2T>C intron 2 splice donor site and an IVS3-1G>A mutation of the SBDS gene (Austin et al, 2005).…”

Section: Figures and Tablementioning

confidence: 99%

Disease-Specific Induced Pluripotent Stem Cells

Park

Arora

Huo

et al. 2008

Cell

2,019

1,532

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Tissue culture of immortal cell strains from diseased patients is an invaluable resource for medical research, but is largely limited to tumor cell lines or transformed derivatives of native tissues. Here we describe the generation of induced pluripotent stem (iPS) cells from patients with a variety of genetic diseases with either Mendelian or complex inheritance that include: adenosine deaminase deficiency-related severe combined immunodeficiency (ADA-SCID), Shwachman-Bodian-Diamond syndrome (SBDS), Gaucher disease (GD) type III, Duchenne (DMD) and Becker muscular dystrophy (BMD), Parkinson disease (PD), Huntington disease (HD), juvenile-onset, type 1 diabetes mellitus (JDM), Down syndrome (DS)/trisomy 21 and the carrier state of Lesch-Nyhan syndrome. Such patient-specific stem cells offer an unprecedented opportunity to recapitulate both normal and pathologic human tissue formation in vitro, thereby enabling disease investigation and drug development.

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Two new mutations at the adenosine deaminase (ADA) locus (Q254X and del nt1050-54) unusual for not being missense mutations

Cited by 14 publications

References 8 publications

Novel splicing, missense, and deletion mutations in seven adenosine deaminase-deficient patients with late/delayed onset of combined immunodeficiency disease. Contribution of genotype to phenotype.

Novel splicing, missense, and deletion mutations in seven adenosine deaminase-deficient patients with late/delayed onset of combined immunodeficiency disease. Contribution of genotype to phenotype.

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

Disease-Specific Induced Pluripotent Stem Cells

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