title: SNP array and FISH analysis of a proband with a 22q13.2- 22qter duplication shed light on the molecular origin of the rearrangement.
abstract: BACKGROUND
  In about one third of healthy subjects, the microscopic analysis of chromosomes reveals heteromorphisms with no clinical implications: for example changes in size of the short arm of acrocentric chromosomes. In patients with a pathological phenotype, however, a large acrocentric short arm can mask a genomic imbalance and should be investigated in more detail. We report the first case of a chromosome 22 with a large acrocentric short arm masking a partial trisomy of the distal long arm, characterized by SNP array. We suggest a possible molecular mechanism underlying the rearrangement.
  
  
  METHODS
  We report the case of a 15-year-old dysmorphic girl with low grade psychomotor retardation characterized by a karyotype with a large acrocentric short arm of one chromosome 22. Cytogenetic analysis revealed a normal karyotype with a very intense Q-fluorescent and large satellite on the chromosome 22 short arm. Fluorescence in situ hybridisation analysis showed a de novo partial trisomy of the 22q13.2-qter chromosome region attached to the short arm of chromosome 22. SNP-array analysis showed that the duplication was 8.5 Mb long and originated from the paternal chromosome. Haplotype analysis revealed that the two paternal copies of the distal part of chromosome 22 have the same haplotype and, therefore, both originated from the same paternal chromosome 22. A possible molecular mechanism that could explain this scenario is a break-induced replication (BIR) which is involved in non-reciprocal translocation events.
  
  
  CONCLUSIONS
  The combined use of FISH and SNP arrays was crucial for a better understanding of the molecular mechanism underlying this rearrangement. This strategy could be applied for a better understanding of the molecular mechanisms underlying cryptic chromosomal rearrangements.
authors.affiliation: Biology and Genetics Division, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy. chiara.magri@unibs.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Magri
authors.affiliation: Biology and Genetics Division, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy. eleonora.marchina@unibs.it.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Marchina
authors.affiliation: Biology and Genetics Division, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy. valeria.bertini@unibs.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Bertini
authors.affiliation: Biology and Genetics Division, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy. michele.traversa@unibs.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Traversa
authors.affiliation: Biology and Genetics Division, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy. giulia.savio@unibs.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Savio
authors.affiliation: Pediatric Division, Spedali Civili, Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy. genauxo@gmail.com.
authors.forename: Alba
authors.initials: A
authors.lastname: Pilotta
authors.affiliation: Biology and Genetics Division, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy. giovanna.piovani@unibs.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Piovani
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology*; D000293:Adolescent; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D019295:Computational Biology; D005260:Female; D005821:Genetic Techniques; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011596:Psychomotor Disorders / Q000235:genetics / Q000473:pathology*; D014314:Trisomy / Q000235:genetics* / Q000473:pathology