Identification of a submicroscopic 3.2 Mb chromosomal 16q12.2‐13 deletion in a child with short stature, mild developmental delay, and craniofacial anomalies, by high‐density oligonucleotide array‐a recognizable syndrome

Abstract

Interstitial deletion of 16q has emerged into a recognizable pattern of congenital malformation. We report on a 9-year-old boy with short stature, psychomotor retardation, high forehead, broad flat nasal bridge, hypertelorism, cup-shaped ears, short neck, and a normal karyotype. Using high-density oligonucleotide array chip (Affymetrix 6.0) to perform parental and proband samples concurrently on three chips and interpreted as a trio set, a de novo 3.2 Mb deletion from bands q12.2 to q13 on chromosome 16 (from 52.08 to 55.3 Mb) of paternal origin was identified. The deletion was confirmed by quantitative genomic PCR and the break points were defined by junction PCR. Our study demonstrated the power of high-density oligonucleotide array chip in identifying novel submicroscopic deletions that were not detectable using G-banding cytogenetic technology. Furthermore, our result narrowed down the critical region for craniofacial features in interstitial 16q11.2-q13 deletion syndrome. In patients who have high forehead, broad flat nasal bridge, hypertelorism, cup-shaped ears, short neck and short stature, high-density array should be included in initial work up.

A 16q12.2q21 deletion identified in a patient with developmental delay, epilepsy, short stature, and distinctive features

“…Interstitial deletions of the 16q centromeric region are rare and only a small number of patients have been reported (Ballif et al . ; Borgatti et al ; Chang et al ). In this study, we identified a patient with a rare interstitial 16q12.2q21 microdeletion and studied the genotype‐phenotype correlation in comparison with previously reported patients.…”

Two novel genes TOX3 and COL21A1 in large extended Malay families with nonsyndromic cleft lip and/or palate

“…Deletion on 16q12 region has been extensively studied in decades in relation to syndromic cases with various phenotypes and one of the craniofacial anomalies identified was high‐arched palate or cleft of the soft palate (Callen et al, ; Chang et al, ; Elder, Ferguson, & Lockhart, ; Shoukier et al, ). Therefore, there is high possibility that this mutation also occurred in nonsyndromic cleft cases but the specific mechanism of action of TOX3 confers craniofacial deformity risk was unclear.…”

A 16q12 microdeletion in a boy with severe psychomotor delay, craniofacial dysmorphism, brain and limb malformations, and a heart defect

“… Schematic representation of the 16q12.1q12.2 deletion in our patient and previously published reports of patients with overlapping deletions. The bi‐directional arrow indicates the SROs and OMIM genes (bottom) in Patients 1, 2 [Ballif et al, 2008], 3 [Bardakjian et al, 2009], 4 [Borozdin et al, 2006], 5 [Matthaei et al, 2005], and a partially overlapping deletion in 16q12.2‐q13 that was published recently by Chang et al [2010] (patient 6). The clinical details are summarized in Table I.…”

“…Haploinsufficiency of the ZNF423 gene has also been postulated as the underlying cause of intellectual disability and other features associated with microdeletions of 16q11.2q12.2 [Ballif et al, 2008]. In addition, Chang et al [2010] recently published a 3.2‐Mb deletion in bands 16q12.2 to q13 in a child with short stature, mild developmental delay, and craniofacial anomalies.…”