Segmental haplosufficiency: transmitted deletions of 2p12 include a pancreatic regeneration gene cluster and have no apparent phenotypic consequences

• Published in: European journal of human genetics : EJHG Vol. 13; no. 3; pp. 283 - 291
• Main Authors: BARBER, John C. K, THOMAS, N. Simon, LUNDSTEEN, Claes, COLLINSON, Morag N, DENNIS, Nick R, LIEHR, Thomas, WEISE, Anja, BELITZ, Britta, PFEIFFER, Lutz, KIRCHHOFF, Maria, KRAG-OLSEN, Bente
• Format: Journal Article
• Language: English
• Published: Avenel, NJ Nature Publishing 01-03-2005; Nature Publishing Group
• Subjects: Adult; Biological and medical sciences; Child, Preschool; Chromosome aberrations; Chromosome Banding; Chromosome Deletion; Chromosomes, Human, Pair 18 - genetics; Chromosomes, Human, Pair 2 - genetics; Female; General aspects. Genetic counseling; Humans; Infant; Karyotyping; Male; Medical genetics; Medical sciences; Multigene Family; Pancreas - physiology; Pedigree; Phenotype; Prenatal Diagnosis; Regeneration - genetics; Sequence Deletion; Trisomy; Wilms Tumor - genetics; United Kingdom; Europe; Gene cluster; transmitted imbalance; www.som.soton.ac.uk/research/geneticsdiv; 2p12; Chromosome; Chromosome Anomaly Collection; haplosufficiency; normal phenotype; Regeneration; Phenotype; Gene; Segmental; Deletion; Collection; Anomaly; Pancreas; REG genes
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/sj.ejhg.5201267

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).