First Report of Low-Rate Mosaicism for 20q11.21q12 Deletion and Delineation of the Associated Disorder

Abstract

Interstitial deletions of the long arm of chromosome 20 are very rare, with only 12 reported patients harboring the 20q11.2 microdeletion and presenting a disorder characterized by psychomotor and growth delay, dysmorphisms, and brachy-/clinodactyly. We describe the first case of mosaic 20q11.2 deletion in a 5-year-old girl affected by mild psychomotor delay, feeding difficulties, growth retardation, craniofacial dysmorphisms, and finger anomalies. SNP array analysis disclosed 20% of cells with a 20q11.21q12 deletion, encompassing the 20q11.2 minimal critical region and the 3 OMIM disease-causing genes GDF5, EPB41L1, and SAMHD1. We propose a pathogenic role of other genes mapping outside the small region of overlap, in particular GHRH (growth hormone releasing hormone), whose haploinsufficiency could be responsible for the prenatal onset of growth retardation which is shared by half of these patients. Our patient highlights the utility of chromosomal microarray analysis to identify low-level mosaicism.

Comparison of karyotype analysis and SNP-array in prenatal diagnosis of mosaicism aneuploidy

“…CNVs found accidentally in SNP-array should be explained in accordance with the guidelines [25]. In prenatal samples, mosaicism detected in uncultured materials is likely to represent the presence of normal and abnormal cell lines in the fetus.Those cases(group II) with apparent mosaic SNP-array results but karyotype of long-term culture failed to detect the abnormal cell line may be due to the discrepancies in cell populations after culture [26].The mosaic rate of karyotype analysis in group I ranged from 2 to 50% with an average of 17% while SNP-array showed no abnormaliltis. Theoretically,SNP-array can detect mosaic rate as low as 5%, but in fact, affected by the experimental process and sample quality, it can only detect mosaicism with a level of more than 20% in the application of prenatal diagnosis [27].That may be the reason why the SNP-array in our study could not detect mosaicism in group I.…”

Clinical and molecular cytogenetic studies of five new patients with 20q11q12 deletion and review of the literature: Proposition of two critical regions

“…Interstitial proximal deletions of the long arm of chromosome 20 (20q11.2q12) are rare, with 16 unrelated patients exhibiting a proximal interstitial 20q deletion reported so far (Callier et al, 2006; Gervasini et al, 2013; Hiraki et al, 2011; Iourov et al, 2013; Iqbal & Al‐Owain, 2007; Jedraszak et al, 2015; Petersen et al, 1987; Posmyk et al, 2014; Santoro et al, 2013; Shabtai et al, 1993). The clinical phenotype of patients with proximal 20q deletions comprises prenatal and postnatal growth retardation, feeding difficulties, psychomotor retardation, intellectual disability, and craniofacial dysmorphisms (Loddo et al, 2018). Anomalies of the extremities like brachydactyly, clinodactyly, and polydactyly have also been reported in patients with 20q proximal deletion syndrome (Hiraki et al, 2011; Jedraszak et al, 2015; Posmyk et al, 2014).…”