Erratum: Detection of six novel FBN1 mutations in British patients affected by Marfan syndrome.

Marfan syndrome (MFS), an autosomal dominant disorder of the extracellular matrix, is due to mutations in fibrillin-1 (FBN1) gene. Investigations carried out in the last decade, unveiled the unpredictability of the site of the mutation, which could be anywhere in the gene. FBN1 mutations have been reported in a spectrum of diseases related to MFS, with no clear evidence for a phenotype-genotype correlation. In this paper we analysed 10 British patients affected by MFS and we were able to characterise five novel missense mutations (C474W, C1402Y, G1987R, C2153Y, G2536R), one novel frameshift mutation (7926delC), one already described mutation (P1424A) and one FBN1 variant (P1148A) classified as a polymorphism in the Asian population. Four out of the five novel missense mutations involved either cysteines or an amino acid conserved in the domain structure. The mutation yield in this study is calculated at 80.0% (8/10), thus indicating that SSCA is a reliable and cost-effective technique for the screening of such a large gene. Our results suggest that this method is reliable to search for FBN1 mutations and that FBN1 screening could be a helpful tool to confirm and possibly anticipate the clinical diagnosis in familial cases.

Detection of six novel FBN1 mutations in British patients affected by Marfan syndrome.

Marfan syndrome (MFS), an autosomal dominant disorder of the extracellular matrix, is due to mutations in fibrillin-1 (FBN1) gene. Investigations carried out in the last decade, unveiled the unpredictability of the site of the mutation, which could be anywhere in the gene. FBN1 mutations have been reported in a spectrum of diseases related to MFS, with no clear evidence for a phenotype-genotype correlation. In this paper we analysed 10 British patients affected by MFS and we were able to characterise five novel missense mutations (C474W, C1402Y, G1987R, C2153Y, G2536R), one novel frameshift mutation (7926delC), one already described mutation (P1424A) and one FBN1 variant (P1148A) classified as a polymorphism in the Asian population. Four out of the five novel missense mutations involved either cysteines or an amino acid conserved in the domain structure. The mutation yield in this study is calculated at 80.0% (8/10), thus indicating that SSCA is a reliable and cost-effective technique for the screening of such a large gene. Our results suggest that this method is reliable to search for FBN1 mutations and that FBN1 screening could be a helpful tool to confirm and possibly anticipate the clinical diagnosis in familial cases. Hum Mutat 18:251, 2001.

Distichiasis-lymphoedema: clinical features, venous function and lymphoscintigraphy.

Distichiasis-lymphoedema is a rare variant of the genetically determined lymphoedemas; distichiasis is the abnormal development of the meibomian glands causing aberrant growth of eyelashes. However, a better understanding of this clinically distinct subgroup may provide useful information on the genetic inheritance of all types of lymphoedema. This report provides phenotype data on a very large family with distichiasis-lymphoedema. Lymphoscintigraphy and light reflection rheography (venous function) were undertaken to identify the phenotype more clearly. As a result of lymphoscintigraphy several subjects were reclassified phenotypically (unaffected or affected) with implications for genetic linkage studies. Associated congenital abnormalities were found and venous abnormalities were almost always present in affected limbs. A dominant inheritance with incomplete penetrance was confirmed.