Prospects of Carrier Screening of Aspartylglucosaminuria in Finland

Hietala, M; Grön, K; Syvänen, Ann‐Christine; Peltonen, Leena; Aula, Pertti

doi:10.1159/000472427

Cited by 28 publications

(9 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We compared the carrier frequency of our group with the frequencies reported in Finnish population studies. [4][5][6][7] We also combined the samples (a total of 4710 Finns, 74 of whom were AGUFin major mutation carriers) in these studies and calculated the prevalence of the AGUFin major mutation in the general Finnish population.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Carriers of the aspartylglucosaminuria genetic mutation and chronic arthritis

Arvio

Laiho²,

Kauppi³

et al. 2002

Annals of the Rheumatic Diseases

View full text Add to dashboard Cite

Objective: To ascertain whether being a carrier of an autosomal recessive disease, aspartylglucosaminuria (AGU), predisposes to chronic arthritis, as does AGU disease. Methods: A group of 173 unrelated patients with rheumatoid arthritis (RA) but with no family members with AGU each gave a blood sample for AGUFin major mutation DNA analysis. A group of 131 AGU carriers who were parents of patients with AGU completed a questionnaire on joint symptoms and gave a blood sample for rheumatoid factor (RF) analysis. Eight RF positive parents with prolonged joint symptoms had a rheumatological evaluation. Results: Six patients (1/28) with RA were carriers of the AGUFin major mutation, whereas the carrier frequency among Finns in general is 1/50 to 1/85. Three AGU carriers had chronic arthritis (2.3%), and 17 (13%) were RF positive; the respective percentages among Finns in general are 1.4% and 5%. Conclusion: As for AGU disease, carrier status may also predispose to chronic arthritis.A spartylglucosaminuria (AGU; McKusick 208400) is an autosomal recessive disorder of glycoprotein degradation resulting from decreased activity of aspartylglucosaminidase (EC 3.5.1.26). The disease is more common in Finns than in other populations, with 240 identified cases; however, cases have been reported in all populations. A single nucleotide change (AGUFin major) in the gene encoding aspartylglucosaminidase results in the amino acid substitution Cys163Ser which is the cause of this condition in almost all Finnish patients.1 This mutation results in misfolding of the enzyme protein, loss of its enzymatic activity, and rapid degradation in the endoplasmic reticulum. Progressive mental retardation is the main symptom, and life span is usually less than 45 years.2 Chronic arthritis is common (7% of female and 4% of male patients) in patients with AGU and is characterised by onset in childhood, seropositivity for rheumatoid factor (RF), and a deforming course.3 Population screening studies on the AGUFin major gene in Finland have shown a carrier frequency of 1 case in 50-85. [4][5][6][7] Thus, in a population of 5 million Finns, over 70 000 are estimated to be carriers of AGU.We screened for AGUFin major carriers among patients with chronic arthritis, and studied the occurrence of chronic arthritis in parents of patients with AGU, to ascertain whether AGUFin major carrier status also predisposes to chronic arthritis. PATIENTS AND METHODSWe created two study groups. The first comprised 173 consecutive unrelated patients from the Rheumatism Foundation Hospital laboratory, who had RF positive rheumatoid arthritis (RA) but no cases of AGU in the family. 8 These 38 men (age range 31-78, mean 43 years) and 135 women (age range 25-78, mean 37.5 years) received a fact sheet and a consent form, which they signed when agreeing to give a blood sample for the AGUFin major mutation DNA test in connection with other laboratory tests. 9 The patients were informed of the test result and its significance, and of the possibility of genetic counselling. We co...

show abstract

Section: Methodsmentioning

confidence: 99%

“…3 Population screening studies on the AGUFin major gene in Finland have shown a carrier frequency of 1 case in 50-85. [4][5][6][7] Thus, in a population of 5 million Finns, over 70 000 are estimated to be carriers of AGU.…”

mentioning

confidence: 99%

Carriers of the aspartylglucosaminuria genetic mutation and chronic arthritis

Arvio

Laiho²,

Kauppi³

et al. 2002

Annals of the Rheumatic Diseases

View full text Add to dashboard Cite

show abstract

“…About 2,200 samples have been studied per year either with direct or linkage analysis. There were about 600 neo plastic samples; 2,800 samples have been studied for car rier screening for aspartylglucosaminuria (AGU) [3], or coagulation factor 5. HLA studies have been performed for disease association and risk assessment.…”

Section: Genetic Laboratoriesmentioning

confidence: 99%

“…that counselling had great or moderate impact on their reproductive plans. Attitudes towards genetic testing of the Finnish population were found to be positive in a nationwide questionnaire study [3,18]. The value of fol low-up for over 10 years in hereditary colorectal carcino ma has been studied [8,19,20], Dimension 7: Consumer Satisfaction National Associations The Finnish Society for Medical Genetics was founded in 1976.…”

Section: Qualitymentioning

confidence: 99%

Genetic Services in Finland

Koskull

Salonen²

1997

Eur J Hum Genet

View full text Add to dashboard Cite

“…As a result, there is excessive accumulation of uncleaved glycoasparagines in lysosomes and elevated metabolite levels in urine. In Finland, the estimated incidence of the disease is 1:18,000, while in other countries, the incidence is unknown [3,4]. Sporadic cases are found in many countries and at least 27 different mutations of the gene exist [5].…”

Section: Introductionmentioning

confidence: 99%