title: Segmental haplosufficiency: transmitted deletions of 2p12 include a pancreatic regeneration gene cluster and have no apparent phenotypic consequences.
abstract: Segmental aneuploidy usually has phenotypic consequences but unbalanced rearrangements without phenotypic consequences have also been reported. In particular, harmless deletions of G-dark bands 5p14 and 16q21 have each been found in more than one independent family. Here, we report two families that were ascertained at prenatal diagnosis and had similar overlapping deletions that removed most of the gene poor G-dark band 2p12. PCR mapping showed that the deletions had a minimum size of 6.1 and 6.9 Mb with at least 13 hemizygous loci including a cluster of six pancreatic islet-regenerating genes. These deletions had no apparent phenotypic consequences in eight family members. In contrast, a third family was ascertained through a child with Wilm's tumour; both the child and his mother had more proximal deletions, developmental delay and some dysmorphic features. The deletion had a minimum size of 5.7 Mb and extended into the gene-rich area of 2p11.2. These results are consistent with the idea that there may be segments of the genome that are consistently haplosufficient. The introduction of higher resolution methods of dosage analysis into diagnostic laboratories is already revealing more transmitted abnormalities of uncertain significance. As a result, published cases of transmitted imbalances have been collected as a guide to the possible significance of such findings in the future (see the 'Chromosome Anomaly Collection' at www.som.soton.ac.uk/research/geneticsdiv).
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire SP2 8BJ, UK. john.barber@salisbury.nhs.uk
authors.forename: John C K
authors.initials: JC
authors.lastname: Barber
authors.forename: N Simon
authors.initials: NS
authors.lastname: Thomas
authors.forename: Morag N
authors.initials: MN
authors.lastname: Collinson
authors.forename: Nick R
authors.initials: NR
authors.lastname: Dennis
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
authors.forename: Anja
authors.initials: A
authors.lastname: Weise
authors.forename: Britta
authors.initials: B
authors.lastname: Belitz
authors.forename: Lutz
authors.initials: L
authors.lastname: Pfeiffer
authors.forename: Maria
authors.initials: M
authors.lastname: Kirchhoff
authors.forename: Bente
authors.initials: B
authors.lastname: Krag-Olsen
authors.forename: Claes
authors.initials: C
authors.lastname: Lundsteen
mesh_terms: D000328:Adult; D002675:Child, Preschool; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007621:Karyotyping; D008297:Male; D005810:Multigene Family; D010179:Pancreas / Q000502:physiology*; D010375:Pedigree; D010641:Phenotype; D011296:Prenatal Diagnosis; D012038:Regeneration / Q000235:genetics*; D017384:Sequence Deletion; D014314:Trisomy; D009396:Wilms Tumor / Q000235:genetics*