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Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations b
Author(s) -
Valstar Marlies J.,
BertoliAvella Aida M.,
Wessels Marja W.,
Ruijter George J.G.,
de Graaf Bianca,
Olmer Renske,
Elfferich Peter,
Neijs Sanne,
Kariminejad Roxana,
Suheyl Ezgü Fatih,
Tokatli Aysegul,
Czartoryska Barbara,
Bosschaart Ad N.,
van den BosTerpstra 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.
Publication year - 2010
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21234
Subject(s) - missense mutation , nonsense mutation , biology , mucopolysaccharidosis , genetics , mutation , mutation testing , compound heterozygosity , gene , microbiology and biotechnology , biochemistry
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. © 2010 Wiley‐Liss, Inc.