Identification of two new missense mutations (R156C and S291L) in two ADA− SCID patients unusual for response to therapy with partial exchange transfusions

  title={Identification of two new missense mutations (R156C and S291L) in two ADA− SCID patients unusual for response to therapy with partial exchange transfusions},
  author={Rochelle Hirschhorn},
  journal={Human Mutation},

Establishing the Molecular Diagnoses in a Cohort of 291 Patients With Predominantly Antibody Deficiency by Targeted Next-Generation Sequencing: Experience From a Monocentric Study

It is reiterated that the immunological heterogeneity of predominantly antibody deficiencies may have a diverse genetic origin, although certain clinical features may hint towards a specific group of defects.

Methods and feasibility study for exome sequencing as a universal second-tier test in newborn screening.

A scalable, exome sequencing-based NGS pipeline with a priori analysis restriction that can be universally applied to any NBS disorder is described, and can be readily expanded to full exome analysis if clinically indicated and parental consent is granted.

Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India

There is an exponential rise in number of cases diagnosed to have SCID over the last 10 years, probably as a result of increasing awareness and improvement in diagnostic facilities at various centers in India.

Heterozygous Mutation in Adenosine Deaminase Gene in a Patient With Severe Lymphopenia Following Corticosteroid Treatment of Autoimmune Hemolytic Anemia

A previously healthy 14-year-old girl with acute onset autoimmune hemolytic anemia is described, associated with severe but transient lymphopenia during corticosteroid therapy, without infectious episodes during follow-up, and a heterozygous ADA gene mutation is detected.

Diagnosis, Treatment and Long-Term Follow Up of Patients with ADA Deficiency: a Single-Center Experience

A more rapid recovery was observed in enzyme replacement treated patients in comparison with those transplanted that, however, showed a continuous and long-lasting improvement both in terms of immune and metabolic recovery.

Adenosine deaminase: Functional implications and different classes of inhibitors

A number of ADA inibitors have been designed and synthesized, classified as ground‐state and transition‐state inhibitors, which may be used to mimic the genetic deficiency of the enzyme, in lymphoproliferative disorders or immunosuppressive therapy, to potentiate the effect of antileukemic or antiviral nucleosides, and, together with adenosine kinase, to reduce breakdown ofadenosine in inflammation, hypertension, and ischemic injury.

Full hematopoietic engraftment after allogeneic bone marrow transplantation without cytoreduction in a child with severe combined immunodeficiency.

Bone marrow transplantation (BMT) for severe combined immunodeficiency (SCID) with human leukocyte antigen (HLA)-identical sibling donors but no pretransplantation cytoreduction results in

Adenosine deaminase deficiency: genotype-phenotype correlations based on expressed activity of 29 mutant alleles.

A quantitative framework and ranking system for relating genotype to phenotype is provided and a strong inverse correlation between red-cell dAXP level and total ADA activity expressed by each patient's alleles in SO3834 is found.

Two newly identified mutations (Thr233Ile and Leu152Met) in partially adenosine deaminase-deficient (ADA–) individuals that result in differing biochemical and metabolic phenotypes

Biochemical findings and a family history suggestive of immunodeficiency in prior offspring support the idea that the Leu152Met mutation could result in disease in homozygous individuals challenged by severe environmental insult or in heterozygosity with a null mutation.



One adenosine deaminase allele in a patient with severe combined immunodeficiency contains a point mutation abolishing enzyme activity.

Cloned and sequenced an adenosine deaminase gene from a patient with severe combined immunodeficiency (SCID) caused by inherited ADA deficiency showed that the mutation at position 304 is responsible for ADA inactivation.

Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase.

It is concluded that from the standpoints of efficacy, convenience, and safety, polyethylene glycol-modified adenosine deaminase is preferable to red-cell transfusion as a treatment forAdenosineDeaminase deficiency.

Progress toward gene therapy.

  • R. Blaese
  • Medicine, Biology
    Clinical immunology and immunopathology
  • 1991

Homozygosity for a newly identified missense mutation in a patient with very severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID).

This mutation in homozygous form appears to be associated with very severe disease, since the patient had perinatal onset of clinical manifestations of SCID, the highest concentration of the toxic metabolite deoxyATP in nine patients studied, and a relatively poor immunologic response during the initial 2 years of therapy with polyethylene glycol-adenosine deaminase.

Five missense mutations at the adenosine deaminase locus (ADA) detected by altered restriction fragments and their frequency in ADA--patients with severe combined immunodeficiency (ADA-SCID).

It is reported that 5 missense mutations account for one third of the ADA--chromosomes studied, with 2 mutations being relatively common.

Enzyme replacement therapy for adenosine deaminase deficiency and severe combined immunodeficiency.

Frozen irradiated plasma, which alone had no effect on lymphocytes numbers or responses, promoted lymphocytosis when given with frozen irradiated red blood cells, suggesting enzyme replacement therapy may provide a way to treat patients with adenosine deaminase deficiency associated with severe combined immunodeficiency disease who do not have histocompatible bone-marrow donors.

Identification and characterization of nine RFLPs at the adenosine deaminase (ADA) locus.

Nine RFLPs at the adenosine deaminase (ADA) locus are identified and/or characterized, detected by digestion of DNA with MspI, BanII, PstI, BalI, and PvuII, and two additional haplotypes not found in the normal population were identified in homozygous form in patients.

A high proportion of ADA point mutations associated with a specific alanine-to-valine substitution.

A conservative amino acid substitution is found in a high proportion of patients with ADA deficiency; this can easily be detected by Southern analysis.

Hot spot mutations in adenosine deaminase deficiency.

There is thus a very high frequency of hot spot mutations in partial ADA deficiency, and most of these children carry two different mutant alleles, which were able to correlate genotype and phenotype and to dissect the activity of individual mutant allele.