The mutation p.Ser298Pro in the sulphamidase gene (SGSH) is associated with a slowly progressive clinical phenotype in mucopolysaccharidosis type IIIA (Sanfilippo A syndrome)
Standard
The mutation p.Ser298Pro in the sulphamidase gene (SGSH) is associated with a slowly progressive clinical phenotype in mucopolysaccharidosis type IIIA (Sanfilippo A syndrome). / Meyer, Ann; Kossow, Kai; Gal, Andreas; Steglich, Cordula; Mühlhausen, Chris; Ullrich, Kurt; Braulke, Thomas; Muschol, Nicole.
in: HUM MUTAT, Jahrgang 29, Nr. 5, 5, 05.2008, S. 770.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - The mutation p.Ser298Pro in the sulphamidase gene (SGSH) is associated with a slowly progressive clinical phenotype in mucopolysaccharidosis type IIIA (Sanfilippo A syndrome)
AU - Meyer, Ann
AU - Kossow, Kai
AU - Gal, Andreas
AU - Steglich, Cordula
AU - Mühlhausen, Chris
AU - Ullrich, Kurt
AU - Braulke, Thomas
AU - Muschol, Nicole
PY - 2008/5
Y1 - 2008/5
N2 - Mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo A syndrome) is caused by mutations in the N-sulfoglucosamine sulfohydrolase (SGSH) gene and the resulting defective lysosomal degradation of the glycosaminoglycan heparan sulfate. The onset and progression of the disease are highly variable. Seventy-five mutations distributed over the SGSH gene have been described. We here report on the analysis of the natural course of the disease in 54 MPS IIIA patients through the use of a detailed questionnaire and four-point scoring system and an examination of the underlying mutations. By assessing the degree of developmental regression over time a group of seven patients with a slowly progressive course of the disease were identified. In these seven patients and in 3 other mildly affected patients the missense mutation c.892T>C (p.Ser298Pro) was found on one allele. These patients showed a lower frequency and later onset of the typical symptoms of the disease. The onset of regression in speech abilities and cognitive functions were delayed by 0.7 and 0.8 years, respectively, and the onset of regression of motor functions occurred 6.1 years later than in all other MPS IIIA patients. Severe regression in speech, cognitive and motor functions were delayed by 5, 5.9, and 11.2 years, respectively. These data suggest that in MPS IIIA patients carrying the mutation p.Ser298Pro a slowly progressive phenotype can be predicted and this may have an important impact on parental counselling and therapeutic interventions.
AB - Mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo A syndrome) is caused by mutations in the N-sulfoglucosamine sulfohydrolase (SGSH) gene and the resulting defective lysosomal degradation of the glycosaminoglycan heparan sulfate. The onset and progression of the disease are highly variable. Seventy-five mutations distributed over the SGSH gene have been described. We here report on the analysis of the natural course of the disease in 54 MPS IIIA patients through the use of a detailed questionnaire and four-point scoring system and an examination of the underlying mutations. By assessing the degree of developmental regression over time a group of seven patients with a slowly progressive course of the disease were identified. In these seven patients and in 3 other mildly affected patients the missense mutation c.892T>C (p.Ser298Pro) was found on one allele. These patients showed a lower frequency and later onset of the typical symptoms of the disease. The onset of regression in speech abilities and cognitive functions were delayed by 0.7 and 0.8 years, respectively, and the onset of regression of motor functions occurred 6.1 years later than in all other MPS IIIA patients. Severe regression in speech, cognitive and motor functions were delayed by 5, 5.9, and 11.2 years, respectively. These data suggest that in MPS IIIA patients carrying the mutation p.Ser298Pro a slowly progressive phenotype can be predicted and this may have an important impact on parental counselling and therapeutic interventions.
KW - Adolescent
KW - Adult
KW - Child
KW - Child, Preschool
KW - Disease Progression
KW - Female
KW - Genotype
KW - Humans
KW - Hydrolases/genetics
KW - Infant
KW - Infant, Newborn
KW - Male
KW - Mucopolysaccharidosis III/genetics
KW - Mutation
KW - Phenotype
KW - Proline/genetics
KW - Serine/genetics
U2 - 10.1002/humu.20738
DO - 10.1002/humu.20738
M3 - SCORING: Zeitschriftenaufsatz
C2 - 18407553
VL - 29
SP - 770
JO - HUM MUTAT
JF - HUM MUTAT
SN - 1059-7794
IS - 5
M1 - 5
ER -