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.
Department of Clinical Genetics, Erasmus University Medical Center, Dr. Molewaterplein 50, Rotterdam, The Netherlands.
Marlies J
MJ
Valstar
Aida M
AM
Bertoli-Avella
Marja W
MW
Wessels
George J G
GJ
Ruijter
Bianca
B
de Graaf
Renske
R
Olmer
Peter
P
Elfferich
Sanne
S
Neijs
Roxana
R
Kariminejad
Fatih
F
Suheyl Ezgü
Aysegul
A
Tokatli
Barbara
B
Czartoryska
Ad N
AN
Bosschaart
Feikje
F
van den Bos-Terpstra
Hugues
H
Puissant
Friederike
F
Bürger
Heymut
H
Omran
D
D
Eckert
Mirella
M
Filocamo
Emil
E
Simeonov
Patrick J
PJ
Willems
Ron A
RA
Wevers
Martinus F
MF
Niermeijer
Dicky J J
DJ
Halley
Ben J H M
BJ
Poorthuis
Otto P
OP
van Diggelen
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