Compound-heterozygous Marfan syndrome

被引：23

作者：

Van Dijk, F. S. ^{[1
]}

Hamel, B. C. ^{[2
]}

Hilhorst-Hofstee, Y. ^{[3
]}

Mulder, B. J. M. ^{[4
,5
]}

Timmermans, J. ^{[6
]}

Pals, G. ^{[1
]}

Cobben, J. M. ^{[7
]}

机构：

[1] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands

[3] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands

[4] Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands

[5] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands

[6] Radboud Univ Nijmegen, Med Ctr, Dept Cardiol, NL-6525 ED Nijmegen, Netherlands

[7] Univ Amsterdam, Acad Med Ctr, Dept Pediat, NL-1105 AZ Amsterdam, Netherlands

来源：

EUROPEAN JOURNAL OF MEDICAL GENETICS | 2009年 / 52卷 / 01期

关键词：

Compound heterozygous; Marfan syndrome; FBN1; mutation; MUTATION; PHENOTYPE; GENETICS;

D O I：

10.1016/j.ejmg.2008.11.004

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We report two families in which the probands have compound-heterozygous Marfan syndrome (MFS). The proband of family I has the R2726W FBN1 mutation associated with isolated skeletal features on one allele and a pathogenic FBN1 mutation on the other allele. The phenotype of the compound-heterozygous probands appears to be more severe than that of their heterozygous family members which underlines the possibility that certain trans-located FBN1 mutations might act as modifiers of phenotype explaining some of the intrafamilial variability in Marfan syndrome. (C) 2008 Elsevier Masson SAS. All rights reserved.

引用

页码：1 / 5

页数：5

共 14 条

[1] Molecular genetics of Marfan syndrome [J].

Boileau, C ;

Jondeau, G ;

Mizuguchi, T ;

Matsumoto, N .

CURRENT OPINION IN CARDIOLOGY, 2005, 20 (03) :194-200

[2] The FBN1 (R2726W) mutation is not fully penetrant [J].

Buoni, S ;

Zannolli, R ;

Macucci, F ;

Ansaldi, S ;

Grasso, M ;

Arbustini, E ;

Fois, A .

ANNALS OF HUMAN GENETICS, 2004, 68 :633-638

[3] Determination of the molecular basis of Marfan syndrome: a growth industry [J].

Byers, PH .

JOURNAL OF CLINICAL INVESTIGATION, 2004, 114 (02) :161-163

[4] Update of the UMD-FBN1 mutation database and creation of an FBN1 polymorphlism database [J].

Collod-Béroud, G ;

Le Bourdelles, S ;

Ades, L ;

Ala-Kokko, L ;

Booms, P ;

Boxer, M ;

Child, A ;

Comeglio, P ;

De Paepe, A ;

Hyland, JC ;

Holman, K ;

Kaitila, I ;

Loeys, B ;

Matyas, G ;

Nuytinck, L ;

Peltonen, L ;

Rantamaki, T ;

Robinson, P ;

Steinmann, B ;

Junien, C ;

Béroud, C ;

Boileau, C .

HUMAN MUTATION, 2003, 22 (03) :199-208

[5] Homozygosity for a FBN1 missense mutation: clinical and molecular evidence for recessive Marfan syndrome [J].

de Vries, Bert B. A. ;

Pals, Gerard ;

Odink, Roelof ;

Hamel, Ben C. J. .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2007, 15 (09) :930-935

[6] Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome [J].

Habashi, JP ;

Judge, DP ;

Holm, TM ;

Cohn, RD ;

Loeys, BL ;

Cooper, TK ;

Myers, L ;

Klein, EC ;

Liu, GS ;

Calvi, C ;

Podowski, M ;

Neptune, ER ;

Halushka, MK ;

Bedja, D ;

Gabrielson, K ;

Rifkin, DB ;

Carta, L ;

Ramirez, F ;

Huso, DL ;

Dietz, HC .

SCIENCE, 2006, 312 (5770) :117-121

[7] Allelic variation in normal human FBN1 expression in a family with Marfan syndrome:: a potential modifier of phenotype? [J].

Hutchinson, S ;

Furger, A ;

Halliday, D ;

Judge, DP ;

Jefferson, A ;

Dietz, HC ;

Firth, H ;

Handford, PA .

HUMAN MOLECULAR GENETICS, 2003, 12 (18) :2269-2276

[8]

Judge DP, 2005, LANCET, V366, P1965, DOI 10.1016/S0140-6736(05)67789-6

[9] Evidence for a critical contribution of haploinsufficiency in the complex pathogenesis of Marfan syndrome [J].

Judge, DP ;

Biery, NJ ;

Keene, DR ;

Geubtner, J ;

Myers, L ;

Huso, DL ;

Sakai, LY ;

Dietz, HC .

JOURNAL OF CLINICAL INVESTIGATION, 2004, 114 (02) :172-181

[10]

KARTTUNEN L, 1994, AM J HUM GENET, V55, P1083

← 1 2 →