Abstract
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 inframe 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.
| Original language | English |
|---|---|
| Journal | Human Mutation |
| Volume | 31 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2010 |
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Keywords
- α-N-acetylglucosamine- 6-sulphate sulphatase
- α-N-acetylglucosamine-6-sulphatase
- GNS
- Mucopolysaccharidosis IIID
- Mutations
- Sanfilippo syndrome
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
Mucopolysaccharidosis type IIID : 12 new patients and 15 novel mutations. / Valstar, Marlies J.; Bertoli-Avella, Aida M.; Wessels, Marja W.; Ruijter, George J G; De Graaf, Bianca; Olmer, Renske; Elfferich, Peter; Neijs, Sanne; Kariminejad, Roxana; Ezgü, Fatih Suheyl; Tokatli, Aysegul; Czartoryska, Barbara; Bosschaart, Ad N.; Van Den Bos-Terpstra, Feikje; Puissant, Hugues; Bürger, Friederike; Omran, Heymut; Eckert, D.; Filocamo, Mirella; Simeonov, Emil; Willems, Patrick J.; Wevers, Ron A.; Niermeijer, Martinus F.; Halley, Dicky J J; Poorthuis, Ben J H M; Van Diggelen, Otto P.
In: Human Mutation, Vol. 31, No. 5, 05.2010.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mucopolysaccharidosis type IIID
T2 - 12 new patients and 15 novel mutations
AU - Valstar, Marlies J.
AU - Bertoli-Avella, Aida M.
AU - Wessels, Marja W.
AU - Ruijter, George J G
AU - De Graaf, Bianca
AU - Olmer, Renske
AU - Elfferich, Peter
AU - Neijs, Sanne
AU - Kariminejad, Roxana
AU - Ezgü, Fatih Suheyl
AU - Tokatli, Aysegul
AU - Czartoryska, Barbara
AU - Bosschaart, Ad N.
AU - Van Den Bos-Terpstra, Feikje
AU - Puissant, Hugues
AU - Bürger, Friederike
AU - Omran, Heymut
AU - Eckert, D.
AU - Filocamo, Mirella
AU - Simeonov, Emil
AU - Willems, Patrick J.
AU - Wevers, Ron A.
AU - Niermeijer, Martinus F.
AU - Halley, Dicky J J
AU - Poorthuis, Ben J H M
AU - Van Diggelen, Otto P.
PY - 2010/5
Y1 - 2010/5
N2 - 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 inframe 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.
AB - 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 inframe 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.
KW - α-N-acetylglucosamine- 6-sulphate sulphatase
KW - α-N-acetylglucosamine-6-sulphatase
KW - GNS
KW - Mucopolysaccharidosis IIID
KW - Mutations
KW - Sanfilippo syndrome
UR - http://www.scopus.com/inward/record.url?scp=77951817853&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77951817853&partnerID=8YFLogxK
U2 - 10.1002/humu.21234
DO - 10.1002/humu.21234
M3 - Article
C2 - 20232353
AN - SCOPUS:77951817853
VL - 31
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 5
ER -