title: ISPD gene homozygous deletion identified by SNP array confirms prenatal manifestation of Walker-Warburg syndrome.
abstract: Walker-Warburg syndrome (WWS) is a rare form of autosomal recessive, congenital muscular dystrophy that is associated with brain and eye anomalies. Several genes encoding proteins involved in abnormal α-dystroglycan glycosylation have been implicated in the aetiology of WWS, most recently the ISPD gene. Typical WWS brain anomalies, such as cobblestone lissencephaly, hydrocephalus and cerebellar malformations, can be prenatally detected through routine ultrasound examinations. Here, we report two karyotypically normal foetuses with multiple brain anomalies that corresponded to WWS symptoms. Using a SNP-array examination on the amniotic fluid DNA, a homozygous microdeletion was identified at 7p21.2p21.1 within the ISPD gene. Published data and our findings led us to the conclusion that a homozygous segmental intragenic deletion of the ISPD gene causes the most severe phenotype of Walker-Warburg syndrome. Our results also clearly supports the use of chromosomal microarray analysis as a first-line diagnostic test in patients with a foetus with one or more major structural abnormalities identified on ultrasonographic examination.
authors.affiliation: Gennet, Centre for Fetal Medicine, Praha, Czech Republic. Electronic address: marie.trkova@gennet.cz.
authors.forename: Marie
authors.initials: M
authors.lastname: Trkova
authors.affiliation: Gennet, Centre for Fetal Medicine, Praha, Czech Republic.
authors.forename: Vera
authors.initials: V
authors.lastname: Krutilkova
authors.affiliation: Gennet, Centre for Fetal Medicine, Praha, Czech Republic.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Smetanova
authors.affiliation: Gennet, Centre for Fetal Medicine, Praha, Czech Republic.
authors.forename: Vera
authors.initials: V
authors.lastname: Becvarova
authors.affiliation: Gennet, Centre for Fetal Medicine, Praha, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Hlavova
authors.affiliation: Gennet, Centre for Fetal Medicine, Praha, Czech Republic.
authors.forename: Nada
authors.initials: N
authors.lastname: Jencikova
authors.affiliation: Gennet, Centre for Fetal Medicine, Praha, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Hodacova
authors.affiliation: Gennet, Centre for Fetal Medicine, Praha, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Hnykova
authors.affiliation: Gennet, Centre for Fetal Medicine, Praha, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Hroncova
authors.affiliation: Gennet, Centre for Fetal Medicine, Praha, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Horacek
authors.affiliation: Gennet, Centre for Fetal Medicine, Praha, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Stejskal
mesh_terms: D000025:Abortion, Eugenic; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002897:Chromosomes, Human, Pair 7; D005190:Family; D005260:Female; D005333:Fetus; D017353:Gene Deletion; D015870:Gene Expression; D006720:Homozygote; D006801:Humans; D059785:Karyotype; D009713:Nucleotidyltransferases / Q000172:deficiency / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016216:Ultrasonography, Prenatal; D058494:Walker-Warburg Syndrome / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology
chemical_list: D009713:Nucleotidyltransferases; C573136:CRPPA protein, human
keywords: 7p21 microdeletion; Brain anomalies; ISPD gene; SNP array; Walker–Warburg syndrome