WWOX-related encephalopathies: delineation of the phenotypical spectrum and emerging genotype-phenotype correlation

摘要: Background Homozygous mutations in WWOX were reported eight individuals of two families with autosomal recessive spinocerebellar ataxia type 12 and siblings infantile epileptic encephalopathy (IEE), including one who deceased prior to DNA sampling. Methods By combining array comparative genomic hybridisation, targeted Sanger sequencing next generation sequencing, we identified five further patients from four IEE due biallelic alterations . Results We deleterious alleles consisting deletions, a base-pair frameshifting deletion, missense nonsense mutations. Genotype-phenotype correlation emerges the seven families. The phenotype carrying predicted null was characterised by (1) little if any psychomotor acquisitions, poor spontaneous motility absent eye contact birth, (2) pharmacoresistant epilepsy starting 1st weeks life, (3) possible retinal degeneration, acquired microcephaly premature death. This contrasted less severe hypomorphic alleles. In line this correlation, allele mutation intermediate. Conclusions Our results obtained combination different molecular techniques undoubtedly incriminate as gene for illustrate usefulness high throughput data mining identification genes rare disorders. structure locus encompassing FRA16D fragile site might explain why constitutive deletions are recurrently genetic databases, suggesting that -related encephalopathies, although likely rare, may not be exceptional.