Interstitial 6q25 microdeletion syndrome: ARID1B is the key gene

Abstract

Interstitial deletions of the long arm of chromosome 6 are rare. Clinically, these deletions are considered to be part of a unique microdeletion syndrome associated with intellectual disability and speech impairment, typical dysmorphic features, structural anomalies of the brain, microcephaly, and non-specific multiple organ anomalies. The critical region for the interstitial 6q microdeletion phenotype was mapped to 6q24-6q25, particularly the 6q25.3 region containing the genes ARID1B and ZDHHC14. It has been hypothesized that haploinsufficiency of these genes impairs normal development of the brain and is responsible for the phenotype. This case report describes a girl presenting with typical features of 6q microdeletion syndrome, including global developmental delay, speech impairment, distinct dysmorphic features, dysgenesis of the corpus callosum, common limb anomalies, and hearing loss. Chromosome analysis by array-CGH revealed a small interstitial 6q deletion spanning approximately 1.1 Mb of DNA and containing only one coding gene, ARID1B. We suggest that ARID1B is the key gene behind 6q microdeletion syndrome, and we discuss its possible role in the phenotypic manifestations.

Interstitial 6q25 microdeletion syndrome: 46,XX,del(6)(q25.2q26)

“…Array CGH with the SurePrint G3 CGH+SNP 4 × 180K microarray (Agilent Technologies, Santa Clara, CA, USA) showed a 10.2 Mb deletion at q25.2‐q26 (position, 154242746‐164462426; Human GRCh37/hg19; Fig. g), which contains a common chromosome region to that mentioned in previous reports . Genetic analysis of the parents was normal.…”

“…(f) G‐banding analysis of chromosome 6. (g) Range of chromosome deletion in each previous case of interstitial 6q25 microdeletion syndrome . Nine cases from the top are from Ref.…”

Multiple Congenital Anomalies and Global Developmental Delay in a Patient with Interstitial 6q25.2q26 Deletion: A Diagnostic Odyssey

“…The boy's clinical features overlap with several features of these patients. The most common ones include developmental or cognitive delay of varying degree, distinctive facial features, hypotonia and hirsutism, broad nasal bridge with broad nasal tip, thick eyebrows, and long eyelashes as well as congenital anomalies including malformations of the gastrointestinal, genitourinary, and/or central nervous systems [Nagamani et al, 2009;Michelson et al, 2012;Ronzoni et al, 2016].…”

“…Some of the common phenotypic findings in these patients include dysmorphic facial features, brain anomalies, and genital anomalies [Eash et al, 2005;Nagamani et al, 2009]. On the other hand, smaller deletions of approximately 1 Mb involving just the 6q25.3 region have been found to be associated with dysgenesis of the corpus callosum and hearing loss [Ronzoni et al, 2016].…”

Necrotizing Enterocolitis in Two Siblings and an Unrelated Infant with Overlapping Chromosome 6q25 Deletions

“…Interstitial deletions of 6q were first reported in 1975 and are more commonly characterized by developmental delay, ear anomalies, hypotonia, and postnatal growth retardation [Milosević and Kalicanin, 1975;Nagamani et al, 2009]. Critical regions for interstitial 6q deletions have also been proposed, specifically the 6q25.3 region which contains the ARID1B gene [Ronzoni et al, 2016]. The 3 cases we report include 1 patient with an interstitial deletion of 6q and 2 siblings with an unbalanced translocation resulting in a terminal deletion of 6q.…”