title: The clinical, molecular, and pathological characterisation of a family with two cases of lethal perinatal type 2 Gaucher disease.
abstract: It has recently been emphasised that a subset of patients with type 2 Gaucher disease die in the neonatal period. This report describes an Afghani family with two conceptuses having severe, prenatally detected Gaucher disease. Mutational analysis showed that the family carried a known complex allele which included mutations at amino acids L444P, A456P, and V460V. Although glucocerebrosidase RNA was present, an affected fetus had virtually no glucocerebrosidase cross reactive material on western analyses. The severe clinical course and pathology observed in these patients resemble that of the null allele Gaucher mouse, and suggest that the absence of glucocerebrosidase activity results in early death.
authors.affiliation: National Institute of Mental Health, NIH, Bethesda, MD, USA.
authors.forename: E
authors.initials: E
authors.lastname: Sidransky
authors.forename: N
authors.initials: N
authors.lastname: Tayebi
authors.forename: B K
authors.initials: BK
authors.lastname: Stubblefield
authors.forename: W
authors.initials: W
authors.lastname: Eliason
authors.forename: A
authors.initials: A
authors.lastname: Klineburgess
authors.forename: G P
authors.initials: GP
authors.lastname: Pizzolato
authors.forename: J N
authors.initials: JN
authors.lastname: Cox
authors.forename: J
authors.initials: J
authors.lastname: Porta
authors.forename: A
authors.initials: A
authors.lastname: Bottani
authors.forename: C D
authors.initials: CD
authors.lastname: DeLozier-Blanchet
mesh_terms: D000346:Afghanistan / Q000208:ethnology; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D005776:Gaucher Disease / Q000145:classification / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005804:Genes, Lethal; D005808:Genes, Recessive; D005962:Glucosylceramidase / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010641:Phenotype
chemical_list: D005962:Glucosylceramidase