4 research outputs found
A novel detrimental homozygous mutation in the WFS1 gene in two sisters from nonconsanguineous parents with untreated diabetes insipidus
Given the limited lifespan and with the recent progress in experimental treatments for WS, timely diagnosis and multidisciplinary treatment for DI/DM, hydronephrosis, and visual/psychiatric status-maintaining quality of life-are of crucial importance
Novel NPC1 mutations with different segregation in two related Greek patients with Niemann-Pick type C disease: molecular study in the extended pedigree and clinical correlations
International audienceAbstractBackgroundNiemann-Pick type C disease (NPC) is an autosomal recessive, neurovisceral, lysosomal storage disorder with protean and progressive clinical manifestations, resulting from mutations in either of the two genes, NPC1 (~95% of families) and NPC2. Contrary to other populations, published evidence regarding NPC disease in Greece is sparse.MethodsThe study population consisted of two Greek NPC patients and their extended pedigree. Patientsā clinical, biochemical, molecular profiles and the possible correlations are presented. Genotyping was performed by direct sequencing. Mutationsā origin was investigated through selected exonic NPC1 polymorphisms encountered more frequently in a group of 37 Greek patients with clinical suspicion of NPC disease and in a group of 90 healthy Greek individuals, by the use of Haplore software.ResultsTwo novel NPC1 mutations, [IVS23ā+ā3insT (c.3591ā+ā3insT) and p. K1057R (c.3170Aā>āC)] were identified and each mutation was associated with a specific haplotype. One of the patients was entered to early treatment with miglustat and has presented no overt neurological impairment after 11.5Ā years.ConclusionsThe splicing mutation IVS23ā+ā3insT was associated in homozygocity with a severe biochemical and clinical phenotype. A possible founder effect for this mutation was demonstrated in the Greek Island, as well as a different origin for each novel mutation. Longitudinal follow-up may contribute to clarify the possible effect of early miglustat therapy on the patient compound heterozygous for the two novel mutations
Novel NPC1 mutations with different segregation in two related Greek patients with Niemann-Pick type C disease: molecular study in the extended pedigree and clinical correlations
Background: Niemann-Pick type C disease (NPC) is an autosomal recessive,
neurovisceral, lysosomal storage disorder with protean and progressive
clinical manifestations, resulting from mutations in either of the two
genes, NPC1 (similar to 95% of families) and NPC2. Contrary to other
populations, published evidence regarding NPC disease in Greece is
sparse.
Methods: The study population consisted of two Greek NPC patients and
their extended pedigree. Patientsā clinical, biochemical, molecular
profiles and the possible correlations are presented. Genotyping was
performed by direct sequencing. Mutationsā origin was investigated
through selected exonic NPC1 polymorphisms encountered more frequently
in a group of 37 Greek patients with clinical suspicion of NPC disease
and in a group of 90 healthy Greek individuals, by the use of Haplore
software.
Results: Two novel NPC1 mutations, [IVS23 + 3insT (c.3591 + 3insT) and
p.K1057R (c.3170A > C)] were identified and each mutation was associated
with a specific haplotype. One of the patients was entered to early
treatment with miglustat and has presented no overt neurological
impairment after 11.5 years.
Conclusions: The splicing mutation IVS23 + 3insT was associated in
homozygocity with a severe biochemical and clinical phenotype. A
possible founder effect for this mutation was demonstrated in the Greek
Island, as well as a different origin for each novel mutation.
Longitudinal follow-up may contribute to clarify the possible effect of
early miglustat therapy on the patient compound heterozygous for the two
novel mutations