Gain of FAM123B and ARHGEF9 in an Obese Man with Intellectual Disability, Congenital Heart Defects and Multiple Supernumerary Ring Chromosomes

摘要: In a 24-year-old man with mild intellectual disability, congenital heart defects and obesity, we identified up to 4 small supernumerary marker chromosomes (sSMCs) in blood metaphases. The ring-shaped sSMCs were derived from 11, 12 X as well fourth, unidentified chromosome. interphase nuclei of epithelial cells the urinary tract buccal mucosa, presence r(11), r(12) r(X) was confirmed by FISH. Using Illumina Infinium 317K SNP-arrays, detected 3 copies pericentromeric regions X. present 84–89% various tissues examined, lacks XIST gene, but contains FAM123B, potential dosage-sensitive candidate gene for cardiac abnormalities, ARHGEF9, disability. ARHGEF9 encodes collybistin (CB), which is required localization inhibitory receptor-anchoring protein gephyrin formation maintenance postsynaptic GABAA glycine receptors. We propose that 2-fold increase dosage disturbs stoichiometry CB its interacting proteins at postsynapses. SNP alleles short tandem repeat markers on r(11) compatible maternal origin both through meiosis II error. may have resulted predivision chromatid nondisjunction, leading anaphase lagging, followed incomplete degradation chromosomes.