Wolf-Hirschhorn 综合征：胎儿面部裂和前轴多指畸形中 4p 远端缺失（4p16.1→pter）的从头发生和分子细胞遗传学特征。
Wolf-Hirschhorn syndrome: Prenatal diagnosis and molecular cytogenetic characterization of a de novo distal deletion of 4p (4p16.1 → pter) in a fetus with facial cleft and preaxial polydactyly.
机构信息
Department of Obstetrics and Gynecology, MacKay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Institute of Clinical and Community Health Nursing, National Yang-Ming University, Taipei, Taiwan; Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Department of Obstetrics and Gynecology, MacKay Memorial Hospital, Taipei, Taiwan.
出版信息
Taiwan J Obstet Gynecol. 2020 May;59(3):425-431. doi: 10.1016/j.tjog.2020.03.016.
OBJECTIVE
We present prenatal diagnosis and molecular cytogenetic characterization of Wolf-Hirschhorn syndrome (WHS) in a fetus with facial cleft and preaxial polydactyly.
MATERIALS AND METHODS
A 37-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age, and the result showed an aberrant chromosome 4 or 46,XX,add(4) (p15.3). The woman consulted our clinics at 22 weeks of gestation and requested for repeat amniocentesis. Prenatal ultrasound revealed intrauterine growth restriction, facial cleft, vermian hypoplasia of cerebellum, micrognathia and absent stomach. Conventional cytogenetic analysis was performed on cultured amniocytes, parental bloods and cord blood. Array comparative genomic hybridization (aCGH) and quantitative fluorescent polymerase chain reaction (QF-PCR) were performed on the DNAs extracted from uncultured amniocytes and parental bloods. Fluorescence in situ hybridization (FISH) analysis was performed on cultured metaphase amniocytes.
RESULTS
aCGH analysis on uncultured amniocytes revealed arr 4p16.3p16.1 (74,447-8,732,731) × 1.0 [GRCh37 (hg19)] with an 8.66-Mb deletion of 4p16.3-p16.1 encompassing 70 [Online Mendelian Inheritance of in Man (OMIM)] genes including ZNF141, FGFRL1, TACC3, LETM1, NSD2 and NELFA. QF-PCR revealed a paternal origin of the distal 4p deletion. Conventional cytogenetic analysis revealed 46,XX,del(4) (p16.1)dn in the fetus. Metaphase FISH analysis confirmed a 4p16 deletion. The parental karyotypes were normal. The pregnancy was subsequently terminated, and a malformed fetus was delivered with typical WHS facial dysmorphism, bilateral cleft lip and palate, and preaxial polydactyly on the right hand.
CONCLUSION
aCGH, QF-PCR and FISH help to delineate the nature of a prenatally defected aberrant chromosome, and the acquired information is useful for genetic counseling.
目的
我们呈现了一例面部裂隙和前轴多指畸形胎儿的沃尔夫-赫希霍恩综合征（WHS）的产前诊断和分子细胞遗传学特征。
材料和方法
一位 37 岁的女性因高龄接受了 18 周的羊膜穿刺术，结果显示染色体 4 或 46,XX,add(4) (p15.3)异常。该女性在 22 周妊娠时就诊于我们的诊所，并要求再次进行羊膜穿刺术。产前超声显示宫内生长受限、面部裂隙、小脑蚓部发育不良、小下颌和胃缺如。对培养的羊膜细胞、父母血液和脐带血进行了常规细胞遗传学分析。对未培养的羊膜细胞和父母血液提取的 DNA 进行了微阵列比较基因组杂交（aCGH）和定量荧光聚合酶链反应（QF-PCR）。对培养的中期羊膜细胞进行了荧光原位杂交（FISH）分析。
结果
未培养的羊膜细胞的 aCGH 分析显示 arr 4p16.3p16.1 (74,447-8,732,731)×1.0 [GRCh37 (hg19)]，4p16.3-p16.1 缺失 8.66-Mb，包含 70 个 [在线孟德尔遗传在线 (OMIM)] 基因，包括 ZNF141、FGFRL1、TACC3、LETM1、NSD2 和 NELFA。QF-PCR 显示远端 4p 缺失来源于父系。常规细胞遗传学分析显示胎儿为 46,XX,del(4) (p16.1)dn。中期 FISH 分析证实了 4p16 缺失。父母的核型正常。妊娠随后终止，分娩出一畸形胎儿，具有典型的 WHS 面部畸形、双侧唇腭裂和右手前轴多指畸形。
结论
aCGH、QF-PCR 和 FISH 有助于描绘产前缺陷异常染色体的性质，获得的信息对遗传咨询很有用。
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