Spectrum of CLN6 mutations in variant late infantile neuronal ceroid lipofuscinosis
| Autor: | Ruth E Williams, JD Sharp, K. Parker, RB Wheeler, Sara E. Mole, R. Mark Gardiner |
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| Rok vydání: | 2003 |
| Předmět: |
Genetic Markers
Male Reading Frames Batten disease Population DNA Mutational Analysis Biology Compound heterozygosity medicine.disease_cause Neuronal Ceroid-Lipofuscinoses Genetics medicine Missense mutation Humans Genetic Testing Age of Onset education Child Frameshift Mutation Gene Genetics (clinical) Mutation education.field_of_study Haplotype Genetic Variation Infant Membrane Proteins medicine.disease Alternative Splicing CLN8 Child Preschool Female |
| Zdroj: | Human mutation. 22(1) |
| ISSN: | 1098-1004 |
| Popis: | The neuronal ceroid lipofuscinoses (NCLs) are a group of autosomal recessive neurodegenerative diseases of childhood. CLN6, the gene mutated in variant late infantile NCL (vLINCL), was recently cloned. We report the identification of eight further mutations in CLN6 making a total of 18 reported mutations. These mutations include missense, nonsense, small deletions or insertions, and two splice-site mutations. Ten mutations affect single amino acids, all of which are conserved across vertebrate species. Minor differences in the pattern of disease symptom evolution can be identified. One patient with a more protracted disease progression was a compound heterozygote for a missense mutation and an unidentified mutation. Fifteen CLN6 mutations occur in one or two families only, and families from the same country do not all share the same mutation. Unlike NCLs caused by mutations in CLN1, CLN3, CLN5, and CLN8, there is no major founder mutation in CLN6. However, one mutation (E72X) is significantly more common in patients from Costa Rica than two other mutations present in that same population. In addition, a 1-bp insertion (c.316insC) is associated with families from Pakistan and I154del may be common in Portugal. A group of Roma Gypsy families from the Czech Republic share two disease-associated haplotypes, one of which is also present in a Pakistani family, consistent with the proposed migration of the Roma from the Indian subcontinent 1,000 years ago. All mutations are recorded in the NCL Mutation Database together with their country of origin for use in the development of rapid screening assays to confirm diagnosis and to facilitate carrier testing appropriate to a population. |
| Databáze: | OpenAIRE |
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