title: Clinical application of DNA microarrays: molecular diagnosis and HLA matching of an Amish child with severe combined immune deficiency.
abstract: Amish and Mennonite children with severe combined immune deficiency (SCID) often die without treatment as a result of delayed diagnoses and prohibitive costs of therapy. In this detailed case report, we describe the novel use of DNA microarrays to improve the diagnosis and management of an Amish infant with SCID. Using 10,000 single nucleotide polymorphism (SNP) genotypes from the patient, her parents, and seven siblings, we identified the recombinase activating genes for diagnostic sequencing, and then characterized a novel pathogenic variant in RAG1 (c.2974A>G). The same genotype data were used to identify a sibling stem cell donor who was haplo-identical at human leukocyte antigen (HLA) and blood group (ABO) loci. Autozygosity and linkage analysis of SNP genotypes within a family narrows the search for SCID candidate genes and provides a relatively simple and inexpensive way to identify potential tissue donors among biological siblings.
authors.affiliation: Clinic for Special Children, Strasburg, Pennsylvania 17579, USA. kstrauss@clinicforspecialchildren.org
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Strauss
authors.forename: Erik G
authors.initials: EG
authors.lastname: Puffenberger
authors.forename: Nancy
authors.initials: N
authors.lastname: Bunin
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Rider
authors.forename: Mary C
authors.initials: MC
authors.lastname: Morton
authors.forename: James T
authors.initials: JT
authors.lastname: Eastman
authors.forename: D Holmes
authors.initials: DH
authors.lastname: Morton
mesh_terms: D016026:Bone Marrow Transplantation; D005260:Female; D016654:Genes, RAG-1; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D025202:Molecular Diagnostic Techniques; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy
chemical_list: D006680:HLA Antigens