title: Mosaic monosomy of a neocentric ring chromosome maps brachyphalangy and growth hormone deficiency to 13q31.1-13q32.3.
abstract: We describe a boy with moderate intellectual disability associated with distinctive hand malformations (hypoplastic and angel-shaped middle phalanges) and partial growth hormone (GH) deficiency associated with mosaic deletion of 13q31.1-13q32.3. The deleted segment was mapped to a 20-Mb region bounded by BACs RP11-1143C2 and RP11-139C1, narrowing the previously described locus for hand malformations at this region and suggesting that a locus for GH deficiency is also present at this location. The deleted segment contains at least three candidate genes, glypican-5, FARP1 and SOX21, that may be contributing to the phenotype in this boy. In a significant proportion (approximately 50%) of cells, the deleted region is present as a supernumerary ring chromosome stabilized by the formation of a neocentromere at 13q31-q32, within a region with a known propensity for neocentromere formation. The ring chromosome appears to be prone to low-level misdivision and loss in vitro which, in vivo, must be countered by selection for the balanced karyotype because the level of mosaicism has remained stable over 13 years.
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville 3052, Victoria, Australia. david.amor@mcri.edu.au
authors.forename: David J
authors.initials: DJ
authors.lastname: Amor
authors.forename: Lucille
authors.initials: L
authors.lastname: Voullaire
authors.forename: Karen
authors.initials: K
authors.lastname: Bentley
authors.forename: Ravi
authors.initials: R
authors.lastname: Savarirayan
authors.forename: K H Andy
authors.initials: KH
authors.lastname: Choo
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D002648:Child; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D005385:Fingers / Q000002:abnormalities*; D006130:Growth Disorders / Q000473:pathology; D006228:Hand Deformities, Congenital / Q000473:pathology*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D009006:Monosomy; D009030:Mosaicism; D012303:Ring Chromosomes
chemical_list: D019382:Human Growth Hormone