A germline or de novo mutation in two families with Gaucher disease: implications for recessive disorders.
Gaucher disease (GD) is an autosomal recessive storage disorder that most commonly results from the inheritance of one identifiable mutant glucocerebrosidase (GBA1) allele from each parent. Here, we report two cases of type 2 GD resulting from the inheritance of one identifiable paternal mutant allele and one allele that likely resulted from a maternal germline mutation. Germline mutations or mosiacism are not generally associated with autosomal recessive disorders. The probands from the two unrelated families had the same maternal mutation, leu444pro, that we propose resulted from a de novo maternal germline mutation occurring at this known 'hotspot' for mutation. This first report of a germline mutation for a common point mutation leu444pro (c.1448 T>C;p.leu483pro) in GD has significant implications for molecular diagnostics and genetic counseling in recessive disorders.
Section on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892-3708, USA.
Hamid
H
Saranjam
Sameer S
SS
Chopra
Harvey
H
Levy
Barbara K
BK
Stubblefield
Emerson
E
Maniwang
Ian J
IJ
Cohen
Hagit
H
Baris
Ellen
E
Sidransky
Nahid
N
Tayebi
D005260:Female; D005776:Gaucher Disease / Q000235:genetics*; D018095:Germ-Line Mutation; D005962:Glucosylceramidase / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree
D005962:Glucosylceramidase