PMM2 mutation spectrum, including 10 novel mutations, in a large CDG type 1A family material with a focus on Scandinavian families.
Artikel i vetenskaplig tidskrift, 2000

Carbohydrate-deficient glycoprotein syndrome type IA (CDG IA) is an autosomal recessive disease characterized clinically by severe involvement of the central and peripheral nervous system, and biochemically by complex defects in carbohydrate residues in a number of serum glycoproteins. CDG IA is caused by mutations in the PMM2 gene located in chromosome region 16p13. In this study, 61 CDG type IA patients (122 chromosomes) were screened for mutations in the PMM2 gene using a combination of SSCP and sequence analysis. More than 95% of the mutations could be detected. All of them were missense mutations. Mutations 422G>A and 357C>A were strikingly more common in the material and comprised 58% of mutations detected. Of the 20 mutations found, 10 were not reported previously. Seven mutations, e.g. 26G>A (five alleles) and 548T>C (seven alleles), were found only in Scandinavian families. The most common genotype was 357C>A/422G>A (36%). Three patients were homozygous, 357C>A/357C>A (two cases), and 548T>C/548T>C (one case). No patients homozygous for the most common mutation 422G>A were detected. The different mutations were clustered e.g., in that most were located in exon 5 (five) and exon 8 (six), while no mutation was detected in exon 2. When the frequencies of each mutation were included, exon 5 comprised 61% (65 chromosomes) of the mutations; in Scandinavian patients the frequency of these mutations was 72%. Thus, analysis of exon five in these patients enables both reliable and time-saving first screening in prenatal diagnostic cases. This could be followed by a second step of additional strategies for the detection of other mutations.

Male

Alleles

genetics

Amino Acid Substitution

Scandinavia

Mutation

enzymology

genetics

Genotype

Phosphotransferases (Phosphomutases)

Carbohydrate-Deficient Glycoprotein Syndrome

classification

Female

genetics

epidemiology

Missense

genetics

genetics

Humans

epidemiology

Exons

Författare

Cecilia Bjursell

Göteborgs universitet

Anna Erlandson

Göteborgs universitet

Margareta Nordling

Göteborgs universitet

Staffan Nilsson

Institutionen för matematik, Matematisk statistik

Göteborgs universitet

Jan Wahlström

Göteborgs universitet

Helena Stibler

Bengt Kristiansson

Göteborgs universitet

Tommy Martinsson

Göteborgs universitet

Human Mutation

1059-7794 (ISSN) 1098-1004 (eISSN)

Vol. 16 395-400

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

PubMed

11058896