An Interstitial 20q11.21 Microdeletion Causing Mild Intellectual Disability and Facial Dysmorphisms

Abstract

We report a case of an interstitial chromosome 20q11.21 microdeletion in a 7-year-old male child presenting with mild intellectual disability and facial dysmorphisms. Array comparative genomic hybridization (CGH) has shown that the deletion resulted in the loss of 68 genes, among which 5 genes (COX4I2, MYLK2, ASXL1, DNMT3B, and SNTA1) are disease causing. The size of the deletion was estimated to span 2.6 Mb. Only three cases of deletions encompassing this chromosomal region have been reported. The phenotype of the index patient was found to resemble the mildest cases of Bohring-Opitz syndrome that is caused by ASXL1 mutations. An in silico evaluation of the deleted genomic region has shown that benign genomic variations have never been observed to affect the ASXL1 gene, in contrast to the other disease-causing genes. As a result, it was suggested that ASXL1 loss is likely to be the main cause of the phenotypic manifestations. The present case report indicates that a loss of the disease-causing gene can produce a milder phenotype of a single gene condition.

Clinical and molecular characterization of the 20q11.2 microdeletion syndrome: Six new patients

“…Only five patients with de novo interstitial 20q11.2 deletions have been previously reported, and their cytogenetic results are summarized in Figure [Callier et al, ; Iqbal and Al‐Owain, ; Hiraki et al, ; Gervasini et al, ; Posmyk et al, ]. Another patient reported by Iourov et al [] harboured a more proximal deletion, with a different phenotype, and will be excluded from the discussion.…”

“…Interstitial microdeletions of the chromosome 20q region are rare. To our knowledge, only 17 patients have been reported in the literature to date [Fraisse et al, Petersen et al, ; Porfirio et al, ; Shabtai et al, ; Aldred et al, ; Chen et al, ; Geneviève et al, ; Callier et al, ; Borozdin et al, ; Iqbal and Al‐Owain, ; Hiraki et al, ; Gervasini et al, ; Iourov et al, ; Santoro et al, 2013; Posmyk et al, ] and only six of these patients carried a proximal 20q11.2 deletion, with a size ranging from 2.6 to 6.8 Mb [Callier et al, ; Iqbal and Al‐Owain, ; Hiraki et al, ; Gervasini et al, ; Iourov et al, ; Posmyk et al, ]. Intellectual disability, craniofacial dysmorphism, anomalies of the extremities and feeding difficulties are recurrent clinical features in these patients, suggesting a recognizable microdeletion syndrome.…”

Additional sex combs‐like family genes are required for normal cardiovascular development

“…In addition, mutations in all three ASXL genes have been implicated in solid tumors, such as breast cancer and melanoma (reviewed in Katoh, 2013). Finally, germline mutations of ASXL1, and more recently ASXL3, cause Bohring-Opitz syndrome, a developmental disorder involving craniofacial anomalies, intellectual disability and multiple congenital malformations (Bainbridge et al, 2013;Dinwiddie et al, 2013;Iourov et al, 2013;Hastings et al, 2011;Hoischen et al, 2011;Magini et al, 2012). Both ASXL1 and ASXL2 functionally interact with the histone methyltransferase complex PRC2 and facilitate PRC2 localization to target genes (Abdel-Wahab et al, 2012;Lai and Wang, 2013).…”

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

“…To date, 24 unrelated patients have been reported [Fraisse et al, 1981;Petersen et al, 1987;Porfirio et al, 1987;Shabtai et al, 1993;Aldred et al, 2002;Chen et al, 2005;Genevieve et al, 2005;Callier et al, 2006;Borozdin et al, 2007;Iqbal and Al-Owain, 2007;Hiraki et al, 2011;Gervasini et al, 2013;Iourov et al, 2013;Santoro et al, 2013;Posmyk et al, 2014;Jedraszak et al, 2015;Meredith et al, 2017], including 12 with deletions involving the proximal 20q11.2 region [Callier et al, 2006;Iqbal and Al-Owain, 2007;Hiraki et al, 2011;Gervasini et al, 2013;Iourov et al, 2013;Posmyk et al, 2014;Jedraszak et al, 2015;Meredith et al, 2017]. The clinical phenotype shared by these latter patients includes prenatal and postnatal growth retardation, feeding difficulties, psychomotor retardation and intellectual disability of variable degree, craniofacial dysmorphisms (high forehead, frontal bossing, deep-set eyes, midface hypoplasia), and hand/ feet anomalies such as brachydactyly and clinodactyly.…”