Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations.
Mucopolysaccharidosis III D (Sanfilippo disease type D, MPS IIID) is a rare autosomal recessive lysosomal storage disorder previously described in only 20 patients. MPS IIID is caused by a deficiency of N-acetylglucosamine-6-sulphate sulphatase (GNS), one of the enzymes required for the degradation of heparan sulphate. So far only seven mutations in the GNS gene have been reported. The clinical phenotype of 12 new MPS IIID patients from 10 families was studied. Mutation analysis of GNS was performed in 16 patients (14 index cases). Clinical signs and symptoms of the MPS IIID patients appeared to be similar to previously described patients with MPS III. Early development was normal with onset of behavioral problems around the age of 4 years, followed by developmental stagnation, deterioration of verbal communication and subsequent deterioration of motor functions. Sequence analysis of the coding regions of the gene encoding GNS (GNS) resulted in the identification of 15 novel mutations: 3 missense mutations, 1 nonsense mutation, 4 splice site mutations, 3 frame shift mutations, 3 large deletions and 1 in-frame small deletion. They include the first missense mutations and a relatively high proportion of large rearrangements, which warrants the inclusion of quantitative techniques in routine mutation screening of the GNS gene.
Valstar
Marlies J
MJ
Department of Clinical Genetics, Erasmus University Medical Center, Dr. Molewaterplein 50, Rotterdam, The Netherlands.
Bertoli-Avella
Aida M
AM
Wessels
Marja W
MW
Ruijter
George J G
GJ
de Graaf
Bianca
B
Olmer
Renske
R
Elfferich
Peter
P
Neijs
Sanne
S
Kariminejad
Roxana
R
Suheyl Ezgü
Fatih
F
Tokatli
Aysegul
A
Czartoryska
Barbara
B
Bosschaart
Ad N
AN
van den Bos-Terpstra
Feikje
F
Puissant
Hugues
H
Bürger
Friederike
F
Omran
Heymut
H
Eckert
D
D
Filocamo
Mirella
M
Simeonov
Emil
E
Willems
Patrick J
PJ
Wevers
Ron A
RA
Niermeijer
Martinus F
MF
Halley
Dicky J J
DJ
Poorthuis
Ben J H M
BJ
van Diggelen
Otto P
OP
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D009084:Mucopolysaccharidosis III / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D013429:Sulfatases / Q000172:deficiency* / Q000235:genetics*; D055815:Young Adult
D013429:Sulfatases; C018719:N-acetylglucosamine-6-sulfatase