Novel duplication on chromosome 16 (q12.1-q21) associated with behavioral disorder, mild cognitive impairment, speech delay, and dysmorphic features: case report

Abstract

We report on the 10-year follow-up and clinical, cytogenetic, and molecular investigation of a girl admitted for evaluation because of speech delay, learning difficulties, aggressive behavior, and dysmorphic facial features that included high forehead, round face, epicanthic folds, low-set dysplastic ears, flat nasal bridge, long flat philtrum, thin upper lip, small mouth, and short neck. The analysis of high-resolution GTG- and CTG-banding chromosomes suggested a de novo direct duplication of 16q12-q21 region and fluorescence in situ hybridization analysis with whole-chromosome specific 16 probe confirmed that the duplicated genetic material originated from the chromosome 16. Subsequently, array-based comparative genomic hybridization analysis with a ≈ 75 kb resolution showed a 9.92 Mb gain on the long arm of chromosome 16 at bands q12.1 through q21. To the best of our knowledge, this is the first case of duplication 16q12.1q21 described in literature. Several genes within the duplicated region are possibly correlated with clinical features present in our patient. Clinical and cytogenetic findings were compared with the small number of reported patients with pure duplications 16q, partially overlapping the one in our patient. Clinical phenotype seems to be distinctive between the proximal-intermediate and intermediate-distal regions of the long arm of the chromosome 16. In particular, we observed a set of dysmorphic features that could present a characteristic dup 16q11.2-q13 phenotype. The present study illustrates the advantages of an integrative approach using both conventional and molecular techniques for the precise characterization and genotype-phenotype correlation in patients with dysmorphism, behavioral problems, and learning difficulties.

Distal duplication of chromosome 16q22.1q23.1 in a Vietnamese patient with midface hypoplasia and intellectual disability

“…Duplications of the long arm of chr16 are rare. Currently, there have been 22 cases of pure duplication of chr16q spanning the region from q11 to q24 (Banka, Fitzgibbon, Gaunt, Rankin, & Clayton‐Smith, ; Odak, Barisic, Morozin Pohovski, Riegel, & Schinzel, ). Duplications involving the distal part of chr16q are even less frequent, with only two reported overlapping cases: a 6.1 Mb de novo duplication of chr16q22.1q23.1 in a Japanese boy (Tokutomi et al, ) and a familial 800 Kb microduplication of chr16q22.1 in a family also carrying a chr15q13 microdeletion (Banka et al, ) (Figure e).…”

Copy number variants in hypoplastic right heart syndrome

“…A 7.5 Mb duplication was identified on the long arm of chromosome 16 occupying most of 16q11q12 locus. Previous reports have described an association between large duplications of chromosome 16 and cardiac malformations (Hahm, Chitayat, Iqbal, Cho, & Nitowsky, ; Odak, Barišić, Morožin Pohovski, Riegel, & Schinzel, ). Five genes within the identified duplicated region, RPGRIP1L , RBL2, SALL1, NKD1 , and MYLK3 have been previously linked with heart development and heart abnormalities and could potentially be related to HRHS.…”

A very rare partial trisomy syndrome: De novo duplication of 16q12.1q23.3 in a Turkish girl with developmental delay and facial dysmorphic features

“…To investigate genotype-phenotype correlation, pure partial trisomy 16q cases can be stratified into three groups (proximal, proximal-intermediate, intermediate-distal) according to the location of chromosomal anomaly [ 2 ]. Most cases fall into the proximal 16q duplication group but many reports provide insufficient information about clinical findings and the sizes of duplicated segments characterized by aCGH analysis [ 5 , 6 , 7 ].…”

“…Trisomy 16 is the most common type of autosomal trisomy associated with spontaneous abortion and is incompatible with life [ 1 ]. Among previously reported cases of partial chromosome 16q duplication, the majority presented complex chromosomal abnormalities due to parental balanced chromosomal translocation carriage [ 2 ]. The clinical presentation of very rare pure partial trisomy 16q cases was associated with congenital anomalies, facial dysmorphic findings and intellectual disability [ 3 ].…”