Menke-Hennekam综合征表型及基因型分析  

Clinical characteristics and genetic analysis in Chinese patients with Menke-Hennekam syndrome

作　　者：唐雅楠 叶贤涛 顾学范[1] 余永国[1] 肖冰[1] 孙昱[1] TANG Yanan;YE Xiantao;GU Xuefan;YU Yongguo;XIAO Bing;SUN Yu(Pediatric Endocrinology and Genetic,Shanghai Institute for Pediatric Research,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China)

机构地区：[1]上海交通大学医学院附属新华医院、上海市儿科医学研究所内分泌遗传代谢科,上海200092

出　　处：《临床儿科杂志》2023年第8期613-617,共5页Journal of Clinical Pediatrics

基　　金：国家自然科学基金面上项目(No.81873724);上海市自然科学基金项目(No.20ZR1472700)。

摘　　要：目的探讨CREBBP基因变异所致Menke-Hennekam综合征(MKHK)的临床特征及基因变异特点。方法回顾性总结7例中国MKHK患儿临床特征及基因测序结果。结果7例患儿均有精神发育迟缓、语言及运动发育落后、身材矮小,特殊面容表现为上斜眼睑、内眦距宽、塌鼻梁、短鼻、长人中、招风耳、低耳位、小下颌,2例伴喂养问题,4例伴视力障碍,3例伴听力障碍,3例伴脑发育异常,2例合并手/脚部异常体征。7例患儿携带CREBBP基因的致病/可能致病变异,均位于外显子30和31,共6个不同变异,涉及2种类型基因变异(5个为错义变异、1个为不影响阅读框的插入缺失),全为新发,其中c.5218C>T、c.5225T>A(NM_004380.3)变异尚未有文献报道。结论MKHK是一种罕见的常染色体显性遗传病,大多由CREBBP基因第30或31位外显子杂合错义变异引起。文章报道了CREBBP基因的6个变异,进一步扩大了MKHK的基因变异谱。Objective To explore the clinical phenotype and identify genetic variations in Chinese patients with Menke-Hennekam syndrome(MKHK).Methods The clinical and genetic data of seven children with MKHK were retrospectively analyzed.Results All of the seven children are presented with psychomotor developmental delay,variable degree of intellectual disability,short stature,and facial dysmorphism(including short and upslanted palpebral fissures,telecanthi,depressed nasal bridge,short nose,long philtrum,protruding or low-set ears and micrognathia),accompanied by other manifestations(2/7 feeding problems,4/7 visual impairment,3/7 hearing impairment,3/7 cerebral anomaly,2/7 distal limb malformation).The genetic findings of patientsinvolve six different variants:five missense and one in-frame deletion),all of which arose de novo.c.5218C>T and c.5225T>A(NM_004380.3)variants have not been reported previously in literature.Conclusion MKHK is a rare autosomal dominant genetic disease,most of which are caused by heterozygous missense variation in the end of exon 30 and the beginning of exon 31 of CREBBP.This study revealed six de novo variants of CREBBP,further expanding the genetic spectrum of MKHK.

关 键 词：Menke-Hennekam综合征 Rubinstein-Taybi综合征 智力障碍 发育迟缓 CREBBP基因 基因变异 

分 类 号：R725.9[医药卫生—儿科]