摘要目的:对1例临床表现为癫痫，发育迟缓并倒退的患儿进行临床和遗传学分析。方法:采用荧光底物法分别测定外周血白细胞氨基己糖苷酶A(hexosaminidase A，Hex A)及氨基己糖苷酶A和B(hexosaminidase A&B，Hex A&B)活性。采集患儿及其家系成员的外周血样，应用二代测序技术对患者进行全外显子组测序，并用Sanger测序方法对变异基因的家系分布进行验证。结果:患儿血白细胞Hex A及Hex A&B酶活性下降。患儿 HEXB基因存在杂合变异，变异位点分别为c.1260_1263del和c.1601G>C。患儿母亲、大哥及大姐为c.1260_1263del杂合携带者，c.1601G>C为新生变异，患儿父母、三个哥哥及一个姐姐均未检出该变异。患儿外周血及骨髓细胞学检查均见嗜酸性粒细胞明显增高。 结论:患儿确诊为婴儿型Sandhoff病。 HEXB基因c.1260_1263del和c.1601G>C变异可能是该患儿的病因。嗜酸性粒细胞增多症可见于婴儿型Sandhoff病。

abstractsObjective:To explore the genetic basis for a girl featuring epilepsy, developmental delay and regression.Methods:Clinical data of the patient was collected. Activities of hexosaminidase A(Hex A) and hexosaminidase A&B(Hex A&B) in blood leukocytes were determined by using a fluorometric assay. Peripheral blood samples were collected from the proband and six members from her pedigree. Following extraction of genomic DNA, whole exome sequencing was carried out. Candidate variants were verified by Sanger sequencing.Results:Enzymatic studies of the proband have shown reduced plasma Hex A and Hex A&B activities. Genetic testing revealed that she has carried c. 1260_1263del and c. 1601G>C heterozygous compound variants of the HEXB gene. Her mother, brother and sister were heterozygous carriers of c. 1260_1263del, while her father, mother, three brothers and sister did not carry the c. 1601G>C variant, suggesting that it has a de novo origin. Increased eosinophils were discovered upon cytological examination of peripheral blood and bone marrow samples. Conclusion:The compound heterozygous variants of c. 1260_1263del and c. 1601G>C of the HEXB gene probably underlay the Sandhoff disease in this child. Eosinophilia may be noted in infantile Sandhoff disease.