Unmasking of a hemizygous WFS1 gene mutation by a chromosome 4p deletion of 8.3 Mb in a patient with Wolf–Hirschhorn syndrome

Recurrent copy number changes in mentally retarded children harbour genes involved in cellular localization and the glutamate receptor complex

“…Several of these cases have been described in detail. [39][40][41][42][43][44] In addition, we found nine inherited segmental aneuploidies. The 20 de novo aberrations encompassed 125 BAC probes, 14 of which were also identified as single CNCs shared among at least 2 other patients and 5 among the 48 healthy individuals of our study population.…”

“…However, hemizygosity for a certain gene, as provoked by a copy number loss, may 'unmask' an autosomal-recessive mutation in the retained allele. 12,43 CNCs showing a genomic gain, on the other hand, may contribute to the patient's phenotype if the genes contained therein encode proteins that form heteromeric complexes with other protein(s). Then, the balance of the participating protein components may be perturbed such that nonfunctional complexes with pathogenic consequences may be formed.…”

Discovery of variants unmasked by hemizygous deletions

“…16,17,36 The latter may further increase the phenotypic variability among patients with disorders resulting from structural genome variations. 36 Of note is that in contrast to the patients selected for this study, most reports of unmasking hemizygosity in the literature describe patients who combine two distinct, recognizable syndromes or diseases, such as Prader Willi Syndrome + albinism, 45 Angelman Syndrome + albinism, 46 Smith Magenis Syndrome + sensorineural hearing loss, 47 or Wolf-Hirschhorn syndrome + Wolfram syndrome 48 (see also Supplementary Tables 1 and 2), which may relate to the frequency of the mechanism under study here.…”

An unusual clinical severity of 16p11.2 deletion syndrome caused by unmasked recessive mutation of CLN3

“…Indeed, a review article by Coman and Gardner 17 highlights that this mechanism has already been demonstrated by several authors. [18][19][20][21][22][23] However, to our knowledge, this is the first report of JNCL caused by an unmasked mutation of CLN3 in a 16p11.2-deletion syndrome. This report illustrates the importance of searching for CLN3 mutation when larger 16p11.2 deletion is associated with neurodegenerative features.…”