Abstract
Duplication of the short arm of chromosome 12 is a rare chromosomal abnormality that may arise de novo or result from malsegregation of a balanced parental translocation. This study comprises the clinical description, cytogenetic and cytogenomic analyses and genotype-phenotype correlation in a patient with facial dysmorphism, developmental delay and intellectual impairment caused by non-mosaic partial duplication and a paracentric inversion 12p. The patient’s GTG-banded karyotype was 46,XX,invdup(12)(pter → p13.32::p11.1 → p13.31::p13.31 → qter). A genetic gain of approximately 28 Mb was detected in the chromosomal region arr[GRCh37]12p13.31-p11.1(6914072_34756209)x3. The chromosomal alteration seen in our patient is described as “pure” partial duplication 12p. In most cases, duplication 12p phenotype is characterized by dysmorphic features, multiple congenital anomalies and intellectual disability. A small number of cases in literature have described genes associated with neurodevelopmental disease, such as ING4, CHD4, MFAP5, GRIN2B, SOX5, SCN8A and PIANP. In our patient the duplication 12p was de novo. This study should contribute to the genotype-phenotype correlation in partial duplication 12p cases.
Highlights
Duplication of the short arm of chromosome 12, first described by Uchida and Lin (1973), is a rare chromosomal abnormality with an estimated incidence of 1/50,000 live births (Stengel-Rutkowski et al, 1981)
According to (Allen et al, 1996) cases of duplication 12p can be divided into five categories based on the extent of the region duplicated and whether other chromosomal aneusomies are present
Some dysmorphic features such as sparse hair and eyebrows, hypertelorism, wide and depressed nasal bridge, short nose with wide and anteverted nares, up-slanting palpebral fissures, epicanthic folds, full cheeks, long philtrum, and short neck seen in patients with 12p duplication overlap with patients with Pallister-Killian syndrome (PKS) (OMIM: 601803) (Inage et al, 2010)
Summary
SCN8A and PIANP genes in the 12p12.1 and 12p13.3 regions These genes act in the central nervous system and craniofacial development and are potential candidates for neurological changes in patients with 12p duplication (Poirsier et al, 2014). Most reports of cases of duplication 12p describe the clinical characteristics of the patients and conventional cytogenetics analysis. For six cases of duplication 12p, an array-CGH analysis was performed to refine the chromosomal break points and describe the genes inserted in the duplicated chromosomal region, improving the genotype-phenotype correlation (De Gregori et al, 2005; Hung et al, 2012; Izumi et al, 2012; Liu et al, 2012; Poirsier et al, 2014; Mekkawy et al, 2016). The phenotype-karyotype correlation showed similarities to previously reported cases of partial duplications 12p. Our results contribute to the hypothesis that the 12p13.3 region is responsible for most of the dysmorphic features of duplication 12p
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