Two New de novo Interstitial Duplications Covering 2p14–p22.1: Clinical and Molecular Analysis

Abstract

We provide a detailed clinical and molecular analysis of 2 patients with de novo interstitial duplications at 2p14–p16.1 and 2p16.1–p22.1. The 10.13-Mb duplication of chromosome 2p14–p16.1 was identified in a 9-year-old boy with mental retardation, behavioral problems (hyperactivity, hyperphagia, and subsequent vomiting), recurrent respiratory tract infections, macrocephaly, epilepsy, and dysmorphic features. The 17.49-Mb duplication of 2p16.1–p22.1 was found in a 17-year-old girl with moderate mental retardation, behavioral and emotional problems, anxiety, and facial dysmorphic features. Very few cases of de novo interstitial duplication of 2p14–p22.1 are reported in the literature, with the great majority of them lacking a detailed molecular analysis. The abnormal phenotype of these cases is caused by mechanisms such as the overdose of a duplicated gene (or genes), the disruption of a gene or its regulatory sequence by the breakpoints of duplication, or by an excess of genetic material which may disorganize chromatin conformation affecting distant gene expression. The clinical and molecular analysis of these 2 rare de novo interstitial duplications provides useful information which is extremely valuable for clinical evaluation at the prenatal and postnatal level and for the molecular understanding of the underlying mechanisms of human diseases.

A rare genomic duplication in 2p14 underlies autosomal dominant hearing loss DFNA58

“…The segregation of a duplication involving CNRIP1 in 20 adult patients without significant neurological or mental disorders argues against this hypothesis. The other few reports of duplications in 2p did not overlap with ours or did not indicate their precise physical positions (38)(39)(40). In another recent investigation, hypercalcaemia was described in a patient with 2p13.2-p16.1 duplication and the authors proposed it was associated with PPP3R1 duplication (41).…”

“…Some published studies have reported large duplications involving 2p14. In one study, the authors hypothesized that CNRIP1 overdose, one of the 47 genes duplicated, could be responsible for the neurological and mental disorders due to its wide expression in the central nervous system (38). The segregation of a duplication involving CNRIP1 in 20 adult patients without significant neurological or mental disorders argues against this hypothesis.…”

Severe growth retardation, delayed bone age, and facial dysmorphism in two patients with microduplications in 2p16 → p22

“…Cut‐out from DECIPHER v5.1 showing only cases with duplications overlapping the duplications in our patients and in the patients reported by Kasnauskiene et al [] and Guilherme et al [] ( = short stature, = no short stature, = no information about growth).…”

“…Mégarbané et al [] reviewed the literature for patients with duplication in 2p and found inconsistent phenotypes. However, breakpoints in only few patients were defined by molecular array techniques [Guilherme et al, ; Kasnauskiene et al, ]. Several authors describe growth retardation, cardiopulmonary malformations, and depending on the latter, poor life expectancy.…”

“…The patient reported by Kubo et al [] also showed a large fontanelle, prominent forehead, and hypertelorism similar to our patients. Kasnauskiene et al [] described a 17‐year‐old girl with growth retardation, macrocephaly, developmental delay, and a de novo duplication of 2p16.1–p22.1 (position 40,059,584–57,546,352; NCBI build 36). Although the duplication is telomerically larger than in our patient (approximately 5 Mb and 7 Mb, respectively), the phenotype is very similar (Table ).…”