Missense mutations in FBN1 exons 41 and 42 cause Weill–Marchesani syndrome with thoracic aortic disease and Marfan syndrome. Issue 9 (29th July 2013)

• Record Type: Journal Article
• Authors: Cecchi, Alana; Ogawa, Naomi; Martinez, Hugo R.; Carlson, Alicia; Fan, Yuxin; Penny, Daniel J.; Guo, Dong‐chuan; Eisenberg, Steven; Safi, Hazim; Estrera, Anthony; Lewis, Richard A.; Meyers, Deborah; Milewicz, Dianna M.
• Is Part Of: American journal of medical genetics. Volume 161:Issue 9(2013:Sep.)
• Page Start: 2305
• Page End: 2310
• Publication Date: 2013-07-29
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36044
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="ajmga36044-sec-0001" sec-type="section"> <p>Mutations in <italic>FBN1</italic> cause a range of overlapping but distinct conditions including Marfan syndrome (MFS), Weill–Marchesani syndrome (WMS), familial thoracic aortic aneurysms/dissections (FTAAD), acromicric dysplasia (AD), and geleophysic dysplasia (GD). Two forms of acromelic dysplasia, AD and GD, characterized by short stature, brachydactyly, reduced joint mobility, and characteristic facies, result from heterozygous missense mutations occurring in exons 41 and 42 of <italic>FBN1</italic>; missense mutations in these exons have not been reported to cause MFS or other syndromes. Here we report on probands with MFS and WMS who have heterozygous <italic>FBN1</italic> missense mutations in exons 41 and 42, respectively. The proband with WMS has ectopia lentis, short stature, thickened pinnae, tight skin, striae atrophicae, reduced extension of the elbows, contractures of the fingers and toes, and brachydactyly and has a missense mutation in exon 42 of <italic>FBN1</italic> (c.5242T>C; p.C1748R). He also experienced a previously unreported complication of WMS, an acute thoracic aortic dissection. The second proband displays classic characteristics of MFS, including ectopia lentis, skeletal features, and aortic root dilatation, and has a missense mutation in exon 41 of <italic>FBN1</italic> (c.5084G>A; p.C1695Y). These phenotypes provide evidence that missense mutations in exons 41 and 42 of <italic>FBN1</italic> lead to MFS and WMS in addition to AD and GD and also suggest that all individuals with pathogenic <italic>FBN1</italic> mutations in these exons should be assessed for thoracic aortic disease and ectopia lentis. Further studies are necessary to elucidate the factors responsible for the different phenotypes associated with missense mutations in these exons of <italic>FBN1</italic>. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>