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A.H. Child, P. Comeglio, G. Arno; Phenotype–Genotype Correlation in UK Marfan Syndrome Fibrillin–1 Database . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4630.
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One hundred and seventy mutations in the FBN1 gene have been characterized in UK patients with Marfan syndrome and related disorders. An international FBN1 mutation database (UMD–FBN1) containing over 600 unique mutations is available on line. Accurate molecular diagnosis is useful in long term prognosis, genetic counselling, preventive healthcare, and perimplantation genetic diagnosis (PGD)
We analysed a consecutive series of 447 patients, of which 18 were infants. Peripheral blood genomic DNA was analysed using PCR, SSCP, (295 patients) and/or dHPLC (152 patients), and automatic sequencing of abnormal bands/peaks. A total of 210 relatives (of which 29 were infants) of 82 patients for whom a mutation had been identified were tested for the proband's mutation. Prenatal diagnosis by chorionic villus biopsy was performed four times, and three further couples were referred for PGD.
Mutations in the classic Marfan subgroup were found in 75.8% using SSCP or dHPLC; 92% with dHPLC alone. In incomplete Marfan the yield fell (28.4%). Mutations in patients affected mainly by ectopia lentis (yield 42.8%) were milder and segregated in the first fifteen exons, while mutations in mainly cardiac cases were severe, and scattered throughout the gene. Three out of four pregnancies tested were unaffected and all four pregnancies continued to term.
Ectopia lentis Marfan patients have mild FBN1 mutations mainly in the early exons, while severe cardiac patients' mutations are distributed throughout the sixty–five exons. Mutation analysis aids risk stratification, prenatal and postnatal screening, and PGD for high risk cardiac families.
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