Jain Shobhit, Kim Hyung-Goo, Lacbawan Felicitas, Meliciani Irene, Wenzel Wolfgang, Kurth Ingo, Sharma Josefina, Schoeneman Morris, Ten Svetlana, Layman Lawrence C, Jacobson-Dickman Elka
State University of New York Downstate Medical Center, Children's Hospital at Downstate, Department of Pediatrics, Division of Pediatric Endocrinology, Brooklyn, NY 11203 USA.
Int J Pediatr Endocrinol. 2011 Oct 13;2011(1):11. doi: 10.1186/1687-9856-2011-11.
CHARGE is a phenotypically heterogeneous autosomal dominant disorder recognized as a cohesive syndrome since the identification of CHD7 as a genetic etiology. Classic features include: Coloboma, Heart defects, Atresia choanae, Retarded growth and development, Genitourinary abnormalities, and Ear anomalies and/or deafness. With greater accessibility to genetic analysis, a wider spectrum of features are emerging, and overlap with disorders such as DiGeorge syndrome, Kallmann syndrome, and Hypoparathyroidism Sensorineural Deafness and Renal Disease syndrome, is increasingly evident. We present a patient with a unique manifestation of CHARGE syndrome, including primary hypoparathyroidism and a limb anomaly; to our knowledge, he is also the first CHARGE subject reported with bilateral multicystic dysplastic kidneys. Furthermore, with structural modeling and murine expression studies, we characterize a putative CHD7 G744S missense mutation. Our report continues to expand the CHARGE phenotype and highlights that stringent fulfillment of conventional criteria should not strictly guide genetic analysis.
自将CHD7鉴定为遗传病因以来,CHARGE是一种表型异质性常染色体显性疾病,被认为是一种具有内在联系的综合征。典型特征包括:眼裂、心脏缺陷、后鼻孔闭锁、生长发育迟缓、泌尿生殖系统异常以及耳部异常和/或耳聋。随着基因分析的可及性提高,越来越多的特征出现,并且与诸如狄乔治综合征、卡尔曼综合征以及甲状旁腺功能减退症-感音神经性耳聋和肾病综合征等疾病的重叠越来越明显。我们报告了一名患有CHARGE综合征独特表现的患者,包括原发性甲状旁腺功能减退症和肢体异常;据我们所知,他也是首例报道的患有双侧多囊性发育不良肾的CHARGE患者。此外,通过结构建模和小鼠表达研究,我们对一个推定的CHD7 G744S错义突变进行了特征描述。我们的报告继续扩展了CHARGE的表型,并强调严格满足传统标准不应严格指导基因分析。