title: Severe combined immunodeficiency (SCID): from the detection of a new mutation to preimplantation genetic diagnosis.
abstract: OBJECTIVE
  To describe the identification of a new mutation responsible for causing human severe combined immunodeficiency syndrome (SCID). In a large consanguineous Israeli Arab family, this served as a diagnostic tool and enabled us to carry out preimplantation genetic diagnosis (PGD). We also demonstrated that PGD for homozygosity alleles is feasible.
  
  
  METHODS
  We carried out genome-wide screening followed by fine mapping and linkage analysis in order to identify the candidate genes. We then sequenced DCLRE1C in order to find the familial mutation. The family was anxious to avoid the birth of an affected child, and therefore, because of their religious beliefs, PGD was the only option open to them. The embryos were biopsied at day 3, and a single blastomere from each embryo was analyzed by multiplex polymerase chain reaction for the SCID mutation and 5 additional polymorphic markers flanking DCLRE1C.
  
  
  RESULTS
  Linkage analysis revealed linkage to chromosome 10p13, which harbors the DNA Cross-Link Repair Protein 1 C (DCLRE1C) ARTEMIS gene. Sequencing identified an 8 bp insertion in exon 14 (1306ins8) of DCLRE1C in all the affected patients; this causes an alteration in amino acid 330 of the protein from cysteine to a stop codon (p.C330X). One cycle of PGD was performed and two embryos were transferred, one homozygous wild-type and one a heterozygous carrier, and healthy twins were born.
  
  
  CONCLUSIONS
  Identifying the familial mutation enabled us to design a reliable and accurate PGD protocol, even in this case of a consanguineous family.
authors.affiliation: The Raphael Recanati Genetic Institute, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, 49100, Israel. matarre@clalit.org.il
authors.forename: Reut
authors.initials: R
authors.lastname: Tomashov-Matar
authors.forename: Galia
authors.initials: G
authors.lastname: Biran
authors.forename: Irina
authors.initials: I
authors.lastname: Lagovsky
authors.forename: Neomi
authors.initials: N
authors.lastname: Kotler
authors.forename: Anat
authors.initials: A
authors.lastname: Stein
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fisch
authors.forename: Onit
authors.initials: O
authors.lastname: Sapir
authors.forename: Mordechai
authors.initials: M
authors.lastname: Shohat
mesh_terms: D001483:Base Sequence; D004268:DNA-Binding Proteins; D004720:Endonucleases; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics; D019836:Preimplantation Diagnosis; D017422:Sequence Analysis, DNA; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C426344:DCLRE1C protein, human; D004720:Endonucleases