Idic (Y)(p11.32)性发育异常患者1例的遗传学分析

Genetic analysis for a female carrying idic(Y)(p11.32)with Disorders of sex development

目的探讨1例性发育异常(DSD)患者的遗传学机制。方法选取2022年4月6日因"原发闭经"就诊于临沂市人民医院的1例女性患者作为研究对象。应用染色体核型分析、荧光原位杂交(FISH)、染色体微阵列分析(CMA)、荧光定量PCR、Sanger测序等技术对其进行检测。结果患者为14岁女性,表现为身材矮小、多痣、原发闭经。染色体分析初步判定其核型为46,X,idic(Y)(p11.3)[59]/45,X[39]/47,X,idic(Y)(p11.3)×2[2];FISH检测结果为46,X,der(Y).ish idic(Y)(p11.3)(SRY+)[59]/45,X[39]/47,X,der(Y)×2.ish idic(Y)(p11.3)(SRY+)[2];CMA检测结果为arr[GRCh37](X)×1,(Y)×0-1,arr[GRCh37]Yp11.32(118552_472090)×1,结果显示为45,X[35%]/46,XY[65%]嵌合;荧光探针PCR显示Y染色体AZF区无缺失;Sanger测序未发现SRY基因致病变异。综合各种检测的结果,患者的分子细胞核型被确定为mos 46,X,idic(Y)(p11.32)[59]/45,X[39]/47,X,idic(Y)(p11.32)×2[2].ish 46,X,idic(Y)(p11.32)(DXZ1+,DYZ1++,DYZ3++,SRY+)[59]/45,X(DXZ1+,DYZ1-,DYZ3-,SRY-)[39]/47,X,der(Y)×2.ish idic(Y)(p11.32)(DXZ1+,DYZ1++,DYZ3++,SRY+)[2].arr[GRCh37](X)×1,(Y)×0-1,arr[GRCh37]Yp11.32(118552_472090)×1,判定为携带idic(Y)(p11.32)但表型为女性的嵌合型DSD患者。结论上述嵌合型染色体异常核型可能为该DSD患者的遗传学病因。

Objective To explore the genetic basis for a patient with Disorders of sex development(DSD).Methods A female patient who had presented at the Linyi People′s Hospital due to primary amenorrhea on April 6,2022 was selected as the study subject.Conventional chromosomal karyotyping,fluorescence in situ hybridization(FISH),chromosomal microarray analysis(CMA),fluorescence quantitative PCR and Sanger sequencing were carried out for the patient.Results The patient,a 14-year-old female,had featured short statue,multiple nevi,and primary amenorrhea.She was found to have a karyotype of 46,X,idic(Y)(p11.3)[59]/45,X[39]/47,X,idic(Y)(p11.3)×2[2].The result of FISH assay was 46,X,der(Y).ish idic(Y)(p11.3)(SRY+)[59]/45,X[39]/47,X,der(Y)×2.ish idic(Y)(p11.3)(SRY+)[2].That of CMA was arr[GRCh37](X)×1,(Y)×0-1,arr[GRCh37]Yp11.32(118552_472090)×1.The patient had no deletion in the AZF region of Y chromosome,and was negative for variant of SRY gene.Combining the above results,her molecular karyotype was determined as mos 46,X,idic(Y)(p11.32)[59]/45,X[39]/47,X,idic(Y)(p11.32)×2[2].ish 46,X,idic(Y)(p11.32)(DXZ1+,DYZ1++,DYZ3++,SRY+)[59]/45,X(DXZ1+,DYZ1-,DYZ3-,SRY-)[39]/47,X,der(Y)×2.ish idic(Y)(p11.32)(DXZ1+,DYZ1++,DYZ3++,SRY+)[2].arr[GRCh37](X)×1,(Y)×0-1,arr[GRCh37]Yp11.32(118552_472090)×1.The patient was diagnosed with mosaicism DSD with idic(Y)(p11.32).Conclusion The abnormal mosaicism karyotype probably underlay the DSD in this patient.