TY - JOUR
T1 - Novel mutations in CLN8 in Italian variant late infantile neuronal ceroid lipofuscinosis
T2 - Another genetic hit in the Mediterranean
AU - Cannelli, Natalia
AU - Cassandrini, Denise
AU - Bertini, Enrico
AU - Striano, Pasquale
AU - Fusco, Lucia
AU - Gaggero, Roberto
AU - Specchio, Nicola
AU - Biancheri, Roberta
AU - Vigevano, Federico
AU - Bruno, Claudio
AU - Simonati, Alessandro
AU - Zara, Federico
AU - Santorelli, Filippo M.
PY - 2006/5
Y1 - 2006/5
N2 - Neuronal ceroid lipofuscinoses (NCLs) are autosomal recessive neurodegenerative disorders typically characterized by the accumulation of autofluorescent material in tissues. On the basis of clinical features, age at onset, and molecular genetic defects, it is possible to distinguish at least nine forms. The CLN8 form was first described in Finland, where all the patients are homozygous for a p.Arg24Gly mutation in CLN8. More recently, it has been found that a subset of a Turkish variant of late infantile NCL (v-LINCL) is also associated with CLN8 mutations. To identify the molecular defect in Italian patients with v-LINCL, the CLN8 gene was directly sequenced in 10 patients. Controls were screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Five fluorescent-labeled microsatellite markers covering 1 cM around the gene were used for haplotype analysis. In three Italian v-LINCL patients, identified in a small area in southern Italy, we detected four new mutations in CLN8: c.66delG (p.Gly22fs), c.88G>C (p.Ala30Pro), c.473A>G (p.Tyr158Cys), and c.581A>G (p. Gln194Arg). The single-base deletion was found in two unrelated patients. The novel missense mutations were not identified in ethnically matched control chromosomes. Our findings expand the number of CLN8 variants and corroborate the notion that CLN8 patients are not confined to the Finnish population.
AB - Neuronal ceroid lipofuscinoses (NCLs) are autosomal recessive neurodegenerative disorders typically characterized by the accumulation of autofluorescent material in tissues. On the basis of clinical features, age at onset, and molecular genetic defects, it is possible to distinguish at least nine forms. The CLN8 form was first described in Finland, where all the patients are homozygous for a p.Arg24Gly mutation in CLN8. More recently, it has been found that a subset of a Turkish variant of late infantile NCL (v-LINCL) is also associated with CLN8 mutations. To identify the molecular defect in Italian patients with v-LINCL, the CLN8 gene was directly sequenced in 10 patients. Controls were screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Five fluorescent-labeled microsatellite markers covering 1 cM around the gene were used for haplotype analysis. In three Italian v-LINCL patients, identified in a small area in southern Italy, we detected four new mutations in CLN8: c.66delG (p.Gly22fs), c.88G>C (p.Ala30Pro), c.473A>G (p.Tyr158Cys), and c.581A>G (p. Gln194Arg). The single-base deletion was found in two unrelated patients. The novel missense mutations were not identified in ethnically matched control chromosomes. Our findings expand the number of CLN8 variants and corroborate the notion that CLN8 patients are not confined to the Finnish population.
KW - CLN8
KW - Mutation detection
KW - NCL
KW - Neurodegeneration
KW - v-LINCL
UR - http://www.scopus.com/inward/record.url?scp=33646396485&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646396485&partnerID=8YFLogxK
U2 - 10.1007/s10048-005-0024-y
DO - 10.1007/s10048-005-0024-y
M3 - Article
C2 - 16570191
AN - SCOPUS:33646396485
VL - 7
SP - 111
EP - 117
JO - Neurogenetics
JF - Neurogenetics
SN - 1364-6745
IS - 2
ER -