Sperry Ethan D, Schuette Jane L, van Ravenswaaij-Arts Conny M A, Green Glenn E, Martin Donna M
Department of Human Genetics, The University of Michigan, Ann Arbor, Michigan.
Department of the Medical Scientist Training Program, The University of Michigan, Ann Arbor, Michigan.
Am J Med Genet A. 2016 May;170A(5):1148-54. doi: 10.1002/ajmg.a.37592. Epub 2016 Feb 6.
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.
CHARGE综合征是一种显性疾病，其特征为眼裂、心脏缺陷、后鼻孔闭锁、生长发育迟缓、生殖器发育不全以及耳部异常，包括耳聋和前庭障碍。大多数CHARGE患者在编码CHD7（一种染色质重塑蛋白）的基因中存在致病性变异。在此，我们报告一名15岁女孩，具有CHARGE综合征的临床特征，且在2p25.3 - p25.2处有一个6.5 Mb的新发基因组物质增益。重复区域包含24个基因，包括早期广泛表达的转录因子基因SOX11。对其他28例CHARGE患者的分析显示，没有SOX11拷贝数变化或致病性序列变异。据我们所知，该患儿的染色体异常是独特的，代表了2p25重复与CHARGE综合征临床特征的首次同时出现。我们将我们患者的表型与之前发表的10例孤立性2p末端重复患者进行了比较，并在非典型基因发现的背景下阐述了CHARGE的临床诊断。
