ID
45304
Beschrijving
Principal Investigator: Joseph Roberts, MD, PhD, Duke University, Durham, NC, USA MeSH: Severe Combined Immunodeficiency https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000479 Analysis of the molecular etiologies of severe combined immunodeficiency (SCID) has led to important insights into the control of immune cell development. Most cases of SCID result from either X-linked or autosomal recessive inheritance of mutations in a known causative gene. However, in some cases, the molecular etiology remains unclear. To identify the cause of SCID in a patient known to lack the protein tyrosine phosphatase CD45, we utilized single nucleotide polymorphisms (SNP) arrays and whole exome sequencing. The patient's mother was heterozygous for an inactivating mutation in *CD45*, while the paternal alleles lacked mutations. The patient exhibited a single *CD45* mutation identical to the maternal allele. Patient SNP array analysis revealed no change in copy number but loss of heterozygosity for the entire length of chromosome 1 (Chr1), indicating that disease was caused by uniparental disomy (UPD) with isodisomy of the entire maternal Chr1 bearing the *CD45* mutation. Non-lymphoid blood cells and other mesoderm and ectoderm-derived tissues retained UPD of the entire maternal Chr1 in this patient who had undergone successful bone marrow transplantation. Exome sequencing revealed mutations in 7 additional genes bearing nonsynonymous SNPs predicted to have deleterious effects. These findings represent the first reported case of SCID caused by UPD and suggest UPD should be considered in SCID and other recessive disorders, especially when the patient appears homozygous for an abnormal gene found in only one parent. Evaluation for alterations in other genes affected by UPD should also be considered in such cases.
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- 19-10-22 19-10-22 - Adrian Schulz
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Joseph Roberts, MD, PhD, Duke University, Durham, NC, USA
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19 oktober 2022
DOI
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Creative Commons BY 4.0
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dbGaP phs000479 NHLBI Exome Sequencing in SCID
Eligibility Criteria
- StudyEvent: SEV1
- Eligibility Criteria
- This data table contains subject IDs, consent group information and affection status.
- The data table contains pedigree and gender information of study participants.
- The data table contains mapping of study subject IDs to sample IDs. Samples are the final preps submitted for genotyping, sequencing, and/or expression data. For example, if one patient (subject ID) gave one sample, and that sample was processed differently to generate 2 sequencing runs, there would be two rows, both using the same subject ID, but having 2 unique sample IDs. The data table also includes sample use.
- The subject phenotype data table includes age at diagnosis, serum levels for IgG, IgA, IgM, and IgE, and number of CD45+, CD3+, CD4+, CD8+, TCRab+ T cells, TCRgd+ T cells, CD20+, and CD56+ cells. Data was also collected for proliferation in response to PHA, Con A, PWM, Candida and tetanus.
- The sample attributes data table includes sample type, body site where sample was extracted, sample analyte type and histological type.
- The data table contains a mapping of sample IDs to corresponding GEO accessions.
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Eligibility Criteria
- StudyEvent: SEV1
- Eligibility Criteria
- This data table contains subject IDs, consent group information and affection status.
- The data table contains pedigree and gender information of study participants.
- The data table contains mapping of study subject IDs to sample IDs. Samples are the final preps submitted for genotyping, sequencing, and/or expression data. For example, if one patient (subject ID) gave one sample, and that sample was processed differently to generate 2 sequencing runs, there would be two rows, both using the same subject ID, but having 2 unique sample IDs. The data table also includes sample use.
- The subject phenotype data table includes age at diagnosis, serum levels for IgG, IgA, IgM, and IgE, and number of CD45+, CD3+, CD4+, CD8+, TCRab+ T cells, TCRgd+ T cells, CD20+, and CD56+ cells. Data was also collected for proliferation in response to PHA, Con A, PWM, Candida and tetanus.
- The sample attributes data table includes sample type, body site where sample was extracted, sample analyte type and histological type.
- The data table contains a mapping of sample IDs to corresponding GEO accessions.
C0680251 (UMLS CUI [1,2])