Walker-Warburg syndrome (WWS) is the most severe of a group of congenital disorders, characterized by congenital muscular dystrophy coupled with severe ocular and brain malformations. In at least 1/5 of reported cases, mutations in the protein O-mannosyltransferase 1 (POMT1) gene are associated with this disease, suggesting that the dysfunction of other genes might give rise to WWS. Mutations in the fukutin, fukutin related protein (FKRP), the protein O-mannosyltransferase 2 (POMT2) and very recently in LARGE genes have also been shown to result in WWS. However, mutations in any of these five genes only account for about 25% of WWS patients. Numerous recent studies have demonstrated that the clinical spectrum of the diseases associated with mutations in the fukutin gene is expanding, depending on the type of mutation that arises. In this short report, the authors describe two new mutations in the fukutin gene that cause WWS. The first patient harboured two novel mutations; a point mutation affecting glycine and a deletion in the 3’UTR that affects the polyadenylation signal of the fukutin gene, which could lead to a complete loss of fukutin protein function. These mutations have not been described previously in Fukuyama congenital muscular dystrophy (FCMD), WWS or limb girdle muscular dystrophy (LGMD) patients. The second patient carries a homozygous-single nucleotide insertion that produces a frameshift. This is the first time that this mutation has been detected in a homozygous form in a patient, and appears to give rise to a more severe phenotype compatible with WWS.


Références : Clin Genet. 2008 Feb;73(2):139-45.