Chromosome aberrations involving 10q22: report of three overlapping interstitial deletions and a balanced translocation disrupting C10orf11

Abstract

Interstitial deletions of chromosome band 10q22 are rare. We report on the characterization of three overlapping de novo 10q22 deletions by high-resolution array comparative genomic hybridization in three unrelated patients. Patient 1 had a 7.9 Mb deletion in 10q21.3-q22.2 and suffered from severe feeding problems, facial dysmorphisms and profound mental retardation. Patients 2 and 3 had nearly identical deletions of 3.2 and 3.6 Mb, the proximal breakpoints of which were located at an identical low-copy repeat. Both patients were mentally retarded; patient 3 also suffered from growth retardation and hypotonia. We also report on the results of breakpoint analysis by array painting in a mentally retarded patient with a balanced chromosome translocation 46,XY,t(10;13)(q22;p13)dn. The breakpoint in 10q22 was found to disrupt C10orf11, a brain-expressed gene in the common deleted interval of patients 1-3. This finding suggests that haploinsufficiency of C10orf11 contributes to the cognitive defects in 10q22 deletion patients.

Complex phenotypes blur conventional borders between Say–Barber–Biesecker–Young–Simpson syndrome and genitopatellar syndrome

“…Larger deletions involving KAT6B and other surrounding genes were recorded in three patients (11) and likely also in an older case of a 10q22.1-q22.3 deletion but without defined breakpoints (12). All these patients had developmental delay, intellectual disability and hypertelorism; and at least some were diagnosed with growth deficiency, retarded psychomotor development, absent or reduced speech, hypotonia, sensorineural hearing loss, delayed myelination, post-natal respiratory problems, feeding problems, large anterior fontanel, downslanting palpebral fissures, strabismus, posteriorly rotated ears, short nose, smooth philtrum, microstomia, retrognathia, dental lamina cysts, long/lean/finger-like thumbs, clinodactyly, genital anomalies and diastasis recti.…”

Two de novo Overlapping Interstitial Duplications at 10q22 Associated with Speech Impairments, Behaviour Problems, Genital Anomalies, Developmental Delay and Intellectual Disability

“…However, CNVs at 10q22 are rare given that no LCRs are located in this interval. Only eight patients with de novo deletions at 10q22 have been delineated [7,[11][12][13][14][15], whereas the reciprocal duplications have never been described to date. In this study, we reported two unrelated patients with de novo overlapping duplications at 10q22 separately, who presented with similar clinical features including speech impairments, behavior problems, dysmorphic features, genital anomalies, developmental delay and intellectual disability.…”

“…Numerous studies have shown that KAT6B-related disorders are mainly caused by either nonsense or frameshift mutations in the KAT6B gene that lead to premature truncation of the protein [20][21][22][23][24]. It is noted that individuals with larger 10q22 deletions involving KAT6B gene do not appear to have classic facial features of SBBYSS, but present with some features overlapping those of SBBYSS [7,[11][12][13][14]. Furthermore, Preiksaitiene et al reported a female patient carrying a de novo deletion at 10q22.1q22.3, who presented with immobile mask-like face, blepharophimosis/ptosis, hypotonia, congenital heart defect, developmental delay and intellectual disability which were major features for SBBYSS.…”

“…To date, only eight patients with de novo deletions at 10q22 have been reported, and the main clinical features include speech impairments, dysmorphic features, genital anomalies, intellectual disability and developmental delay [7,[11][12][13][14][15]. Dufke and Han each described a case with a de novo duplication at 10q22.2q22.3~23.1 and 10q22q24 detected by G-banding analysis respectively, whereas the two segments not only covered the 10q22 region but also LCR3-4 which was demonstrated to be clinically significant [8][9][10]16,17].…”

A 10q21.3q22.2 microdeletion identified in a patient with severe developmental delay and multiple congenital anomalies including congenital heart defects

“…The deletion was identified by conventional G-banding. Later, chromosomal microarray testing (CMT) detected similar microdeletions in several other patients (Bartnik et al 2014;Lei et al, 2016;Reddy et al 2011;Tzschach et al 2010).…”