Identification and characterization of a novel homozygous deletion in the alpha-N-acetylglucosaminidase gene in a patient with Sanfilippo type B syndrome (mucopolysaccharidosis IIIB).
Sanfilippo syndrome type B (mucopolysaccharidosis IIIB) is an autosomal recessive disease that is caused by a deficiency of the lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). Over 100 different mutations in the NAGLU gene have been identified in Sanfilippo syndrome type B patients; however, no large deletions have been reported. Here we present the first case of a large homozygous intragenic NAGLU gene deletion identified in an affected child of consanguineous parents. Long range and multiplex PCR methods were used to characterize this deletion which encompasses exons 3 and 4 and is 1146 base pairs long. We propose that Alu element-mediated unequal homologous recombination between an Alu-Y in intron 2 and an Alu-Sx in intron 4 is the likely mechanism for this deletion, thereby contributing further insight into the molecular etiology of this disorder and providing additional evidence of its allelic heterogeneity.
Champion
Kristen J
KJ
Greenwood Genetic Center, 106 Gregor Mendel Circle, Greenwood, SC 29646, USA.
Basehore
Monica J
MJ
Wood
Tim
T
Destrée
Anne
A
Vannuffel
Pascal
P
Maystadt
Isabelle
I
D000118:Acetylglucosaminidase / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D003241:Consanguinity; D005260:Female; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D009084:Mucopolysaccharidosis III / Q000201:enzymology / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion
C033079:alpha-N-acetyl-D-glucosaminidase; D000118:Acetylglucosaminidase