title: A recurrent deletion syndrome at chromosome bands 2p11.2-2p12 flanked by segmental duplications at the breakpoints and including REEP1.
abstract: We identified an identical and recurrent 9.4-Mbp deletion at chromosome bands 2p11.2-2p12, which occurred de novo in two unrelated patients. It is flanked at the distal and proximal breakpoints by two homologous segmental duplications consisting of low copy repeat (LCR) blocks in direct orientation, which have >99% sequence identity. Despite the fact that the deletion was almost 10 Mbp in size, the patients showed a relatively mild clinical phenotype, that is, mild-to-moderate intellectual disability, a happy disposition, speech delay and delayed motor development. Their phenotype matches with that of previously described patients. The 2p11.2-2p12 deletion includes the REEP1 gene that is associated with spastic paraplegia and phenotypic features related to this are apparent in most 2p11.2-2p12 deletion patients, but not in all. Other hemizygous genes that may contribute to the clinical phenotype include LRRTM1 and CTNNA2. We propose a recurrent but rare 2p11.2-2p12 deletion syndrome based on (1) the identical, non-random localisation of the de novo deletion breakpoints in two unrelated patients and a patient from literature, (2) the patients' phenotypic similarity and their phenotypic overlap with other 2p deletions and (3) the presence of highly identical LCR blocks flanking both breakpoints, consistent with a non-allelic homologous recombination (NAHR)-mediated rearrangement.
authors.affiliation: Department Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Servi J C
authors.initials: SJ
authors.lastname: Stevens
authors.affiliation: Department Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Eveline W
authors.initials: EW
authors.lastname: Blom
authors.affiliation: Department Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Ingrid T J
authors.initials: IT
authors.lastname: Siegelaer
authors.affiliation: Department Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Eric E J G L
authors.initials: EE
authors.lastname: Smeets
mesh_terms: D000293:Adolescent; D000483:Alleles; D002675:Child, Preschool; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D056915:DNA Copy Number Variations; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D059765:Homologous Recombination; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D056916:Segmental Duplications, Genomic; D017384:Sequence Deletion; D051178:alpha Catenin / Q000235:genetics
chemical_list: C079671:CTNNA2 protein, human; C526971:LRRTM1 protein, human; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C495318:REEP1 protein, human; D051178:alpha Catenin