Duplication 2p25 in a child with clinical features of CHARGE syndrome

Abstract

CHARGE syndrome is a dominant disorder characterized by ocular colobomata, heart defects, choanal atresia, retardation of growth and development, genital hypoplasia, and ear abnormalities including deafness and vestibular disorders. The majority of individuals with CHARGE have pathogenic variants in the gene encoding CHD7, a chromatin remodeling protein. Here we present a 15-year-old girl with clinical features of CHARGE syndrome and a de novo 6.5 Mb gain of genomic material at 2p25.3-p25.2. The duplicated region contained 24 genes, including the early and broadly expressed transcription factor gene SOX11. Analysis of 28 other patients with CHARGE showed no SOX11 copy number changes or pathogenic sequence variants. To our knowledge, this child’s chromosomal abnormality is unique and represents the first co-occurrence of duplication 2p25 and clinical features of CHARGE syndrome. We compare our patient’s phenotype to ten previously published patients with isolated terminal duplication 2p, and elaborate on the clinical diagnosis of CHARGE in the context of atypical genetic findings.

Partial CHARGE syndrome with bilateral retinochoroidal colobomas associated with 7q11.23 duplication syndrome: case report

“…CHARGE syndrome has been reported in a child with a de novo inverted duplication [ 15 ] (q22q24.3) [ 25 ], in a 6.5 Mb duplication of 2p25 [ 26 ], in duplication 8q and deletion 4q from paternal unbalanced translocation t(4;8)(q34;q22.1) [ 27 ], in de novo balanced t(6;8)(6p8p;6q8q) [ 28 ]; some of these cases predate the availability of clinical sequencing and cannot exclude a co-occuring CDH7 mutation. De novo mutations of CHD7 have been found to occur primarily in the paternal germline, suggesting that imprinting may be involved [ 29 ].…”

Observation of Cleft Palate in an Individual with SOX11 Mutation

“…However, looking at their clinical characteristics, they had features such as nail hypoplasia and abnormal hair distribution that were, in hindsight, consistent with a CSS phenotype. Duplication of SOX11 has recently been identified in a 15-year-old girl with clinical features of CHARGE syndrome (Sperry et al, 2016).…”

Prenatal Diagnosis of Trisomy 2p due to Terminal 2p Duplication including Interstitial Telomeric Sequences

“…Pure partial trisomies 2p have been described more rarely and could result from chromosomal duplications or unbalanced translocations involving the short arms of acrocentric chromosomes. About 15 cases have been reported postnatally [Yunis et al, 1979;Parruti et al, 1989;Mégarbané et al, 1997;Kubo et al, 1999;Roggenbuck et al, 2001;Kochilas et al, 2008;Blassnig-Ezeh et al, 2013;Martinez-Juarez et al, 2014;Sperry et al, 2016] and 4 cases prenatally [Siffroi et al, 1994;Aviram-Goldring et al, 2000, cases 2 and 3;Thangavelu et al, 2004, case 1]. Prenatal findings were recorded between 9 and 32 WG and included anencephaly [Thangavelu et al, 2004], intrauterine growth retardation, small stomach, aortic coarctation [Siffroi et al, 1994], and isolated nuchal translucency [Aviram-Goldring et al, 2000] ( Table 1 ).…”