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.

The novel synaptogenic protein Farp1 links postsynaptic cytoskeletal dynamics and transsynaptic organization

“…This agrees with aberrations of synaptic adhesion molecules and GTPase signaling in developmental and psychiatric disorders (Govek et al, 2005; Südhof, 2008; Penzes et al, 2011). Interestingly, a chromosomal microdeletion that includes the FARP1 gene is also linked to mental retardation (Amor et al, 2005).…”

Sox21 deletion in mice causes postnatal growth deficiency without physiological disruption of hypothalamic-pituitary endocrine axes

“…The contributions of individual genes within the microdeletion to specific features are still not known. One patient with partial GH deficiency was found to have a chromosomal deletion on 13q encompassing SOX21 , FARP1 , and GPC5 (37), although it was not shown whether the loss of SOX21 in this patient was responsible for the growth insufficiency phenotype.…”

A Marfan syndrome‐like phenotype caused by a neocentromeric supernumerary ring chromosome 15

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