title: Detection of an Alu insertion in the POMT1 gene from three French Walker Warburg syndrome families.
abstract: Walker Warburg syndrome (WWS) is the most severe of a group of multiple congenital disorders known as lissencephaly type II ( LIS Type II) associated with congenital muscular dystrophy and eye abnormalities. The POMT1 gene is the most frequently affected found in 20% of patients with WWS. We describe five fetuses with WWS in three non-related families carrying a same mutation in the POMT1 gene. All fetuses presented with tetra ventricular hydrocephaly, and arachnoidal neuroglial ectopia and cortical dysplasia characteristic of LIS type II. We performed sequencing of the POMT1 gene on fetal DNA. The five fetuses were found to share an insertion of an inversed Alu repeated DNA element within exon 3 of the POMT1 gene, all at the heterozygous state except one at the homozygous state. This mutation was associated with a common transition c.2203 C > T (p.Arg735Cys) in exon 20 on the same allele and similar intragenic haplotype, suggesting that the three families could be related or indicating a possible founder effect in France. Insertions of Alu sequences, which are rarely found in coding regions, have occasionally been reported to cause other genetic diseases. However, this is the first report of a retrotransposon insertion in the POMT1 gene associated with WWS.
authors.affiliation: APHP, Bichat Claude-Bernard Hospital, Biochimie métabolique et cellulaire, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Bouchet
authors.forename: S
authors.initials: S
authors.lastname: Vuillaumier-Barrot
authors.forename: M
authors.initials: M
authors.lastname: Gonzales
authors.forename: S
authors.initials: S
authors.lastname: Boukari
authors.forename: C Le
authors.initials: CL
authors.lastname: Bizec
authors.forename: C
authors.initials: C
authors.lastname: Fallet
authors.forename: A-L
authors.initials: AL
authors.lastname: Delezoide
authors.forename: H
authors.initials: H
authors.lastname: Moirot
authors.forename: A
authors.initials: A
authors.lastname: Laquerriere
authors.forename: F
authors.initials: F
authors.lastname: Encha-Razavi
authors.forename: G
authors.initials: G
authors.lastname: Durand
authors.forename: N
authors.initials: N
authors.lastname: Seta
mesh_terms: D000015:Abnormalities, Multiple / Q000201:enzymology* / Q000235:genetics*; D020087:Alu Elements / Q000235:genetics*; D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D001921:Brain / Q000002:abnormalities / Q000196:embryology / Q000201:enzymology; D005124:Eye Abnormalities / Q000201:enzymology / Q000235:genetics; D005260:Female; D005602:France; D006801:Humans; D008364:Mannosyltransferases / Q000235:genetics; D008969:Molecular Sequence Data; D011247:Pregnancy; D013577:Syndrome
chemical_list: D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase