title: Genotype-phenotype correlation in 22q11.2 deletion syndrome.
abstract: BACKGROUND
  The 22q11.2 deletion syndrome (22q11.2DS) is caused by hemizygous microdeletions on chromosome 22q11.2 with highly variable physical and neuropsychiatric manifestations. We explored the genotype-phenotype relationship in a relatively large 22q11.2DS cohort treated and monitored in our clinic using comprehensive clinical evaluation and detailed molecular characterization of the deletion.
  
  
  METHODS
  Molecular analyses in 142 subjects with 22q11.2DS features were performed by FISH and MLPA methods. Participants underwent clinical assessment of physical symptoms and structured psychiatric and cognitive evaluation.
  
  
  RESULTS
  Deletions were found in 110 individuals including one with an atypical nested distal deletion which was missed by the FISH test. Most subjects (88.2%) carried the 3Mb typically deleted region and 11.8% carried 4 types of deletions differing in size and location. No statistically significant genotype-phenotype correlations were found between deletion type and clinical data although some differences in hypocalcemia and cardiovascular anomalies were noted.Analysis of the patient with the distal nested deletion suggested a redundancy of genes causing the physical and neuropsychiatric phenotype in 22q11.2DS and indicating that the psychiatric and cognitive trajectories may be governed by different genes.
  
  
  CONCLUSIONS
  MLPA is a useful and affordable molecular method combining accurate diagnosis and detailed deletion characterization. Variations in deletion type and clinical manifestations impede the detection of significant differences in samples of moderate size, but analysis of individuals with unique deletions may provide insight into the underlying biological mechanisms.Future genotype-phenotype studies should involve large multicenter collaborations employing uniform clinical standards and high-resolution molecular methods.
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Elena
authors.initials: E
authors.lastname: Michaelovsky
authors.forename: Amos
authors.initials: A
authors.lastname: Frisch
authors.forename: Miri
authors.initials: M
authors.lastname: Carmel
authors.forename: Miriam
authors.initials: M
authors.lastname: Patya
authors.forename: Omer
authors.initials: O
authors.lastname: Zarchi
authors.forename: Tamar
authors.initials: T
authors.lastname: Green
authors.forename: Lina
authors.initials: L
authors.lastname: Basel-Vanagaite
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
authors.forename: Doron
authors.initials: D
authors.lastname: Gothelf
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002892:Chromosomes, Human, Pair 22; D015331:Cohort Studies; D004062:DiGeorge Syndrome / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D056726:Genetic Association Studies; D005838:Genotype; D057898:Hemizygote; D006801:Humans; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D010641:Phenotype; D055815:Young Adult