Missense mutations in FBN1 exons 41 and 42 cause Weill-Marchesani syndrome with thoracic aortic disease and Marfan syndrome

Alana Cecchi, Naomi Ogawa, Hugo Martinez, Alicia Carlson, Yuxin Fan, Daniel J. Penny, Dong Chuan Guo, Steven Eisenberg, Hazim Safi, Anthony Estrera, Richard A. Lewis, Deborah Meyers, Dianna M. Milewicz

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Mutations in FBN1 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 FBN1; 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 FBN1 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 FBN1 (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 FBN1 (c.5084G>A; p.C1695Y). These phenotypes provide evidence that missense mutations in exons 41 and 42 of FBN1 lead to MFS and WMS in addition to AD and GD and also suggest that all individuals with pathogenic FBN1 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 FBN1.

Original languageEnglish (US)
Pages (from-to)2305-2310
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume161
Issue number9
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

Fingerprint

Weill-Marchesani Syndrome
Thoracic Diseases
Aortic Diseases
Marfan Syndrome
Missense Mutation
Exons
Ectopia Lentis
Brachydactyly
Phenotype
Mutation
Toes
Contracture
Elbow
Fingers
Acromicric dysplasia
Dissection
Dilatation
Thorax
Joints

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Missense mutations in FBN1 exons 41 and 42 cause Weill-Marchesani syndrome with thoracic aortic disease and Marfan syndrome. / Cecchi, Alana; Ogawa, Naomi; Martinez, Hugo; Carlson, Alicia; Fan, Yuxin; Penny, Daniel J.; Guo, Dong Chuan; Eisenberg, Steven; Safi, Hazim; Estrera, Anthony; Lewis, Richard A.; Meyers, Deborah; Milewicz, Dianna M.

In: American Journal of Medical Genetics, Part A, Vol. 161, No. 9, 01.09.2013, p. 2305-2310.

Research output: Contribution to journalArticle

Cecchi, A, Ogawa, N, Martinez, H, Carlson, A, Fan, Y, Penny, DJ, Guo, DC, Eisenberg, S, Safi, H, Estrera, A, Lewis, RA, Meyers, D & Milewicz, DM 2013, 'Missense mutations in FBN1 exons 41 and 42 cause Weill-Marchesani syndrome with thoracic aortic disease and Marfan syndrome', American Journal of Medical Genetics, Part A, vol. 161, no. 9, pp. 2305-2310. https://doi.org/10.1002/ajmg.a.36044
Cecchi, Alana ; Ogawa, Naomi ; Martinez, Hugo ; Carlson, Alicia ; Fan, Yuxin ; Penny, Daniel J. ; Guo, Dong Chuan ; Eisenberg, Steven ; Safi, Hazim ; Estrera, Anthony ; Lewis, Richard A. ; Meyers, Deborah ; Milewicz, Dianna M. / Missense mutations in FBN1 exons 41 and 42 cause Weill-Marchesani syndrome with thoracic aortic disease and Marfan syndrome. In: American Journal of Medical Genetics, Part A. 2013 ; Vol. 161, No. 9. pp. 2305-2310.
@article{b569fcf45f0c405fa6eedb5872346e48,
title = "Missense mutations in FBN1 exons 41 and 42 cause Weill-Marchesani syndrome with thoracic aortic disease and Marfan syndrome",
abstract = "Mutations in FBN1 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 FBN1; 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 FBN1 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 FBN1 (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 FBN1 (c.5084G>A; p.C1695Y). These phenotypes provide evidence that missense mutations in exons 41 and 42 of FBN1 lead to MFS and WMS in addition to AD and GD and also suggest that all individuals with pathogenic FBN1 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 FBN1.",
author = "Alana Cecchi and Naomi Ogawa and Hugo Martinez and Alicia Carlson and Yuxin Fan and Penny, {Daniel J.} and Guo, {Dong Chuan} and Steven Eisenberg and Hazim Safi and Anthony Estrera and Lewis, {Richard A.} and Deborah Meyers and Milewicz, {Dianna M.}",
year = "2013",
month = "9",
day = "1",
doi = "10.1002/ajmg.a.36044",
language = "English (US)",
volume = "161",
pages = "2305--2310",
journal = "American Journal of Medical Genetics, Part A",
issn = "1552-4825",
publisher = "Wiley-Liss Inc.",
number = "9",

}

TY - JOUR

T1 - Missense mutations in FBN1 exons 41 and 42 cause Weill-Marchesani syndrome with thoracic aortic disease and Marfan syndrome

AU - Cecchi, Alana

AU - Ogawa, Naomi

AU - Martinez, Hugo

AU - Carlson, Alicia

AU - Fan, Yuxin

AU - Penny, Daniel J.

AU - Guo, Dong Chuan

AU - Eisenberg, Steven

AU - Safi, Hazim

AU - Estrera, Anthony

AU - Lewis, Richard A.

AU - Meyers, Deborah

AU - Milewicz, Dianna M.

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Mutations in FBN1 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 FBN1; 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 FBN1 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 FBN1 (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 FBN1 (c.5084G>A; p.C1695Y). These phenotypes provide evidence that missense mutations in exons 41 and 42 of FBN1 lead to MFS and WMS in addition to AD and GD and also suggest that all individuals with pathogenic FBN1 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 FBN1.

AB - Mutations in FBN1 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 FBN1; 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 FBN1 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 FBN1 (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 FBN1 (c.5084G>A; p.C1695Y). These phenotypes provide evidence that missense mutations in exons 41 and 42 of FBN1 lead to MFS and WMS in addition to AD and GD and also suggest that all individuals with pathogenic FBN1 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 FBN1.

UR - http://www.scopus.com/inward/record.url?scp=84881665894&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881665894&partnerID=8YFLogxK

U2 - 10.1002/ajmg.a.36044

DO - 10.1002/ajmg.a.36044

M3 - Article

VL - 161

SP - 2305

EP - 2310

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

SN - 1552-4825

IS - 9

ER -