Two new patients bearing mutations in the fukutin gene confirm the relevance of this gene in Walker-Warburg syndrome

• Published in: Clinical genetics Vol. 73; no. 2; pp. 139 - 145
• Main Authors: Cotarelo, RP, Valero, MC, Prados, B, Peña, A, Rodríguez, L, Fano, O, Marco, JJ, Martínez-Frías, ML, Cruces, J
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-02-2008; Blackwell
• Subjects: 3' Untranslated Regions - genetics; Amino Acid Sequence; Biological and medical sciences; Eye Abnormalities - genetics; Female; Frameshift Mutation; fukutin; Fundamental and applied biological sciences. Psychology; Gene Deletion; General aspects. Genetic counseling; Genetic disorders; Genetics of eukaryotes. Biological and molecular evolution; Genotype & phenotype; Humans; Infant, Newborn; Male; Malformations of the nervous system; Medical genetics; Medical sciences; Membrane Proteins - genetics; Molecular and cellular biology; Molecular Sequence Data; Muscular Dystrophies - genetics; Muscular dystrophy; Mutation; Neurology; Point Mutation; Syndrome; Walker-Warburg syndrome; α-dystroglycanopathies; Human; Nervous system diseases; Neuromuscular diseases; Muscular dystrophy; Genetic disease; Cerebral disorder; Case study; Relevance; Eye disease; Gene; Malformation; Lissencephaly; Central nervous system disease; Genetics; Mutation; α-dystroglycanopathiesfukutin; Walker-Warburg syndrome
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2007.00936.x

Walker–Warburg syndrome (WWS) is an autosomal recessive disorder characterized by congenital muscular dystrophy, brain malformations and structural abnormalities of the eye. We have studied two WWS patients born to non‐consanguineous parents, and in both cases, we identified mutations in the fukutin gene responsible for this syndrome. One of the patients carries a homozygous‐single nucleotide insertion that produces a frameshift, being this the first time that this insertion has been described in homozygosis and causing a WWS phenotype. The other patient carries two novel mutations, one being a point mutation that produces an amino acid substitution, while the other is a deletion in the 3′UTR that affects the polyadenylation signal of the fukutin gene. This deletion would probably result in the complete loss of the fukutin transcripts from this allele. This is the first time a mutation localized outside of the fukutin coding region has been identified as a cause of WWS.