title: Detection of recurrent 4p16.3 microdeletion with 2p25.3 microduplication by multiplex ligation-dependent probe amplification and array comparative genomic hybridization in a fetus from a family with Wolf-Hirschhorn syndrome.
abstract: OBJECTIVE
  We present prenatal diagnosis, genetic counseling, and molecular cytogenetic features of familial recurrence of Wolf-Hirschhorn syndrome (WHS).
  
  
  METHODS
  A 31-year-old woman was referred to a hospital at 24 weeks of gestation because of abnormal ultrasound findings in the fetus. Her first child was a boy who had growth retardation, mental defect, and a distinctive facial appearance. Based on the conventional cytogenetic analysis, the combined use of multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH) facilitated the prenatal diagnosis and genetic counseling in the fetus. Results of the standard G-banging karyotype analysis of the fetus, the parents, and the boy were normal.
  
  
  RESULTS
  The MLPA analysis revealed the same 4p microdeletion accompanied by 2p microduplication in the fetus and the boy. The aCGH analysis revealed a 3.57-Mb 4p16.3 microdeletion or arr [hg19] 4p16.3 (71,552-3,636,893) x1 in the fetus and a 3.29-Mb 4p16.3 microdeletion or arr [hg19] 4p16.3 (71,148-3,360,737) x1 in the boy. The 3.57-Mb 4p16.3 microdeletion encompassed 39 OMIM genes. The 3.29-Mb 4p16.3 microdeletion encompassed 36 OMIM genes. They both included LETM1 and WHSC1. The 2p25.3 microduplication was smaller than 666 kb and encompassed only one OMIM gene, ACP1.
  
  
  CONCLUSIONS
  The combined use of MLPA and aCGH is an effective way to diagnose recurrent WHS. Although WHS is typically caused by a de novo deletion, prenatal diagnosis and genetic counseling are necessary in the next pregnancy in families that have suffered such cases.
authors.affiliation: Department of Central Laboratory, Peking University First Hospital, Number 8 Xi Shi Ku Da Jie, Beijing 100034, China.
authors.forename: Wen-Xu
authors.initials: WX
authors.lastname: Yang
authors.affiliation: Department of Central Laboratory, Peking University First Hospital, Number 8 Xi Shi Ku Da Jie, Beijing 100034, China. Electronic address: panmuren@263.net.
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Central Laboratory, Peking University First Hospital, Number 8 Xi Shi Ku Da Jie, Beijing 100034, China.
authors.forename: Song-Tao
authors.initials: ST
authors.lastname: Wang
authors.affiliation: Department of Central Laboratory, Peking University First Hospital, Number 8 Xi Shi Ku Da Jie, Beijing 100034, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Central Laboratory, Peking University First Hospital, Number 8 Xi Shi Ku Da Jie, Beijing 100034, China.
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Wu
authors.affiliation: Department of Central Laboratory, Peking University First Hospital, Number 8 Xi Shi Ku Da Jie, Beijing 100034, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qi
mesh_terms: D000025:Abortion, Eugenic; D000328:Adult; D002648:Child; D002872:Chromosome Deletion; D058674:Chromosome Duplication; D002889:Chromosomes, Human, Pair 2; D002894:Chromosomes, Human, Pair 4; D055028:Comparative Genomic Hybridization; D005260:Female; D005315:Fetal Diseases / Q000000981:diagnostic imaging / Q000235:genetics*; D005817:Genetic Counseling; D006801:Humans; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D011247:Pregnancy; D016216:Ultrasonography, Prenatal; D054877:Wolf-Hirschhorn Syndrome / Q000000981:diagnostic imaging / Q000235:genetics*
keywords: Wolf–Hirschhorn syndrome; array comparative genomic hybridization; genetic counseling; multiplex ligation-dependent probe amplification; prenatal diagnosis