CD45-deficient severe combined immunodeficiency caused by uniparental disomy

• DOI: 10.1073/pnas.1202249109
• Publication Date: 2012-06-12T05:53:56Z
• Authors: Joseph L. Roberts; Rebecca H. Buckley; Biao Luo; Jianming Pei; Alla Lapidus; Suraj Peri; Qiong Wei; Jinwook Shin; Roberta E. Parrott; Roland L. Dunbrack; Joseph R. Testa; Xiao-Ping Zhong; David L. Wiest
• Keywords: Uniparental disomy; SNP array; Exome; Compound heterozygosity

Analysis of the molecular etiologies SCID has led to important insights into control immune cell development. Most cases result from either X-linked or autosomal recessive inheritance mutations in a known causative gene. However, some cases, etiology remains unclear. To identify cause patient lack protein-tyrosine phosphatase CD45, we used SNP arrays and whole-exome sequencing. The patient's mother was heterozygous for an inactivating mutation CD45 but paternal alleles exhibited no detectable mutations. single identical maternal allele. Patient array analysis revealed change copy number loss heterozygosity entire length chromosome 1 (Chr1), indicating that disease caused by uniparental disomy (UPD) with isodisomy Chr1 bearing mutant Nonlymphoid blood cells other mesoderm- ectoderm-derived tissues retained UPD this patient, who had undergone successful bone marrow transplantation. Exome sequencing seven additional genes nonsynonymous SNPs predicted have deleterious effects. These findings are unique representing reported case suggest should be considered disorders, especially when appears homozygous abnormal gene found only one parent. Evaluation alterations affected also such cases.