Molecular Genetics and Metabolism 90 (2007) 93–96 www.elsevier.com/locate/ymgme 1096-7192/$ - see front matter  2006 Elsevier Inc. All rights reserved. doi:10.1016/j.ymgme.2006.09.005 Detection of an Alu insertion in the POMT1 gene from three French Walker Warburg syndrome families C. Bouchet a , S. Vuillaumier-Barrot a,b,¤ , M. Gonzales c,d , S. Boukari a , C. Le Bizec a , C. Fallet e , A.-L. Delezoide f , H. Moirot g , A. Laquerriere h , F. Encha-Razavi i , G. Durand a , N. Seta a a APHP, Bichat Claude-Bernard Hospital, Biochimie métabolique et cellulaire, Paris, France b CRB3, INSERM U773, Paris, France c APHP, Armand Trousseau Hospital, Department of Genetics and Medical Embryology, Paris, France d University Pierre et Marie Curie, Paris 6, France e APHP, Saint-Anne Hospital, Anapathology, Paris, France f APHP, Robert Debré hospital, Biologie du développement, Paris, France g CHU de Rouen, Unit of Cytogenetics, France h CHU de Rouen, Pathology Laboratory, France i APHP, Necker hospital, Histoembryology, Paris, France Received 17 July 2006; received in revised form 8 September 2006; accepted 8 September 2006 Available online 31 October 2006 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 aVected found in 20% of patients with WWS. We describe Wve 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 Wve 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 hap- lotype, suggesting that the three families could be related or indicating a possible founder eVect 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 Wrst report of a retrotransposon insertion in the POMT1 gene associated with WWS.  2006 Elsevier Inc. All rights reserved. Keywords: Walker Warburg syndrome; Alu insertion; POMT1 Introduction Walker Warburg syndrome (WWS; MIM 236670), a very rare autosomal recessive disorder, is the most severe form of a group of multiple congenital diseases sharing a distinct type of agyria/pachygyria called lissencephaly type II (LIS type II). In these diseases, numerous congenital anomalies have been reported but, as for muscle–eye–brain disease (MEB; MIM 253280) and Fukuyama congenital muscular dystrophy (FCMD; MIM 253800), the most con- sistent are muscle, eye and brain disorders. Brain abnormal- ities are characteristic and include agyria/pachygyria with tetra ventricular hydrocephalus due to obstruction of the meninges and subarachnoid spaces by neuroglial overmi- gration, corpus callosum agenesis/hypoplasia, cerebellar dysplasia and occasionally occipital encephalocele. Patients * Corresponding author. Present address: Laboratoire de Biochimie Métabolisme et Nutrition, Hôpital Bichat-Claude Bernard, 46, rue Henri Huchard, 75877 Paris cedex 18, France. Fax: +33 1 40 25 88 21. E-mail address: sandrine.vuillaumier@bch.aphp.fr (S. Vuillaumier- Barrot).