title: A deletion-insertion mutation in the phosphomannomutase 2 gene in an African American patient with congenital disorders of glycosylation-Ia.
abstract: Congenital disorders of glycosylation (CDG) are a group of metabolic disorders with multisystemic involvement characterized by abnormalities in the synthesis of N-linked oligosaccharides. The most common form, CDG-Ia, resulting from mutations in the gene encoding the enzyme phosphomannomutase (PMM2), manifests with severe abnormalities in psychomotor development, dysmorphic features and visceral involvement. While this disorder is panethnic, we present the first cases of CDG-Ia identified in an African American family with two affected sisters. The proband had failure to thrive in infancy, hypotonia, ataxia, cerebellar hypoplasia and developmental delay. On examination, she also exhibited strabismus, inverted nipples and an atypical perineal fat distribution, all features characteristic of CDG-Ia. Direct sequencing demonstrated that the patient had a unique genotype, T237M/c.565-571 delAGAGAT insGTGGATTTCC. The novel deletion-insertion mutation, which was confirmed by subcloning and sequencing of each allele, introduces a stop codon 11 amino acids downstream from the site of the deletion. The presence of this deletion-insertion mutation at cDNA position 565 suggests that this site in the PMM2 gene may be a hotspot for chromosomal breakage.
authors.affiliation: Clinical Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Nahid
authors.initials: N
authors.lastname: Tayebi
authors.forename: David Q
authors.initials: DQ
authors.lastname: Andrews
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Park
authors.forename: Eduard
authors.initials: E
authors.lastname: Orvisky
authors.forename: John
authors.initials: J
authors.lastname: McReynolds
authors.forename: Ellen
authors.initials: E
authors.lastname: Sidransky
authors.forename: Donna M
authors.initials: DM
authors.lastname: Krasnewich
mesh_terms: D001483:Base Sequence; D044383:Black People / Q000235:genetics; D002675:Child, Preschool; D018981:Congenital Disorders of Glycosylation / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation; D017875:Phosphotransferases (Phosphomutases) / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion; D001741:Black or African American
chemical_list: D017875:Phosphotransferases (Phosphomutases); C052799:phosphomannomutase