title: Prenatal diagnosis and molecular cytogenetic characterization of a derivative chromosome der(18;18)(q10;q10)del(18)(q11.1q12.1)del(18)(q22.1q22.3) presenting as apparent isochromosome 18q in a fetus with holoprosencephaly.
abstract: OBJECTIVE
  To present prenatal diagnosis and molecular cytogenetic characterization of a derivative chromosome der(18;18)(q10;q10)del(18)(q11.1q12.1)del(18)(q22.1q22.3).
  
  
  RESULTS
  A 32-year-old woman was referred for genetic counseling of prenatally detected isochromosome 18q [i(18q)]. She had undergone amniocentesis at 19 gestational weeks because of a trisomy 18 risk of 1/39 derived from abnormally low levels of maternal serum unconjugated estriol, inhibin A, α-fetoprotein, and total β-human chorionic gonadotropin. Amniocentesis revealed a karyotype of 46,XX,i(18)(q10). Parental karyotypes were normal. Prenatal ultrasound showed alobar holoprosencephaly. Repeated amniocentesis was requested and performed at 21 gestational weeks. Array-comparative genomic hybridization analyses revealed a 14-Mb deletion of 18p11.32-p11.21, a 37.8-Mb duplication of 18q12.1-q22.1, and a 6.9-Mb duplication of 18q22.3-q23. Metaphase fluorescence in situ hybridization study showed the absence of an 18q12.1-specific probe signal in one arm and the absence of an 18q22.2-specific probe signal in the other arm of the derivative chromosome. Quantitative fluorescent polymerase chain reaction analysis determined a paternal origin of the derivative chromosome. The cytogenetic result was 46,XX,der(18;18)(q10;q10)del(18)(q11.1q12.1)del(18)(q22.1q22.3). The fetus postnatally manifested cebocephaly.
  
  
  CONCLUSIONS
  Concomitant monosomy 18p and trisomy 18q can be associated with holoprosencephaly and abnormal maternal serum screening results. Array-comparative genomic hybridization, fluorescence in situ hybridization, and quantitative fluorescent polymerase chain reaction are useful in genetic counseling of prenatally detected isochromosomes by providing information on the origin and genetic components of the isochromosome.
authors.affiliation: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan. cpc_mmh@yahoo.com
authors.forename: Chih-Ping
authors.initials: CP
authors.lastname: Chen
authors.forename: Yau-Kun
authors.initials: YK
authors.lastname: Kuo
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Su
authors.forename: Schu-Rern
authors.initials: SR
authors.lastname: Chern
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Pei-Chen
authors.initials: PC
authors.lastname: Wu
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chen
authors.forename: Dai-Dyi
authors.initials: DD
authors.lastname: Town
authors.forename: Wayseen
authors.initials: W
authors.lastname: Wang
mesh_terms: D000328:Adult; D000649:Amniocentesis; D002872:Chromosome Deletion; D002887:Chromosomes, Human, Pair 18; D003937:Diagnosis, Differential; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D016142:Holoprosencephaly / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D006801:Humans; D007621:Karyotyping; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D014314:Trisomy; D014463:Ultrasonography