A novel VEGFR3 mutation causes Milroy disease

被引:35
作者
Butler, Matthew G.
Dagenais, Susan L.
Rockson, Stanley G.
Glover, Thomas W.
机构
[1] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA
[2] Stanford Univ, Sch Med, Stanford, CA 94305 USA
[3] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA
关键词
lymphedema; Milroy disease; VEGFR3;
D O I
10.1002/ajmg.a.31703
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Milroy disease, also known as primary congenital lymphedema, is a hereditary form of lymphedema with autosomal dominant inheritance. Individuals With Milroy disease are typically characterized by congenital onset of lymphedema of the lower limbs due to hypoplasia of the lymphatic vessels. The genetic basis of most cases of Milroy disease has not been established, although mutations in the vascular endothelial growth factor receptor VIEGFR3 (FLT-4) are responsible for some cases with 17 mutations described to date. in this report, we describe a novel VEGFK3 mutation in exon 22 in a four-generation family in which congenital lymphedema segregates in an autosomal dominant manner. in addition to lymphedema, affected family members had other clinical manifestations associated with Milroy disease including hydrocele, ski jump toenails, large caliber veins, and subcutaneous thickening. We screened VEGFR3 for mutations which revealed a novel 3059A > T transversion in exon 22 resulting in Q1020L missense mutation in the second tyrosine kinase domain of VEGFR3. This mutant allele segregated with lymphedema among affected individuals with incomplete penetrance. This is the first report of an exon 22 mutation in Milroy disease. (c) 2007 Wiley-Liss, Inc.
引用
收藏
页码:1212 / 1217
页数:6
相关论文
共 20 条
[1]   Milroy disease and the VEGFR-3 mutation phenotype [J].
Brice, G ;
Child, AH ;
Evans, A ;
Bell, R ;
Mansour, S ;
Burnand, K ;
Sarfarazi, M ;
Jeffery, S ;
Mortimer, P .
JOURNAL OF MEDICAL GENETICS, 2005, 42 (02) :98-102
[2]   A SIMPLE METHOD FOR DNA PURIFICATION FROM PERIPHERAL-BLOOD [J].
CIULLA, TA ;
SKLAR, RM ;
HAUSER, SL .
ANALYTICAL BIOCHEMISTRY, 1988, 174 (02) :485-488
[3]   Hydrops fetalis: an unusual prenatal presentation of hereditary congenital lymphedema [J].
Daniel-Spiegel, E ;
Ghalamkarpour, A ;
Spiegel, R ;
Weiner, E ;
Vikkula, M ;
Shalev, E ;
Shalev, SA .
PRENATAL DIAGNOSIS, 2005, 25 (11) :1015-1018
[4]   Mapping of primary congenital lymphedema to the 5q35.3 region [J].
Evans, AL ;
Brice, G ;
Sotirova, V ;
Mortimer, P ;
Beninson, J ;
Burnand, K ;
Rosbotham, J ;
Child, A ;
Sarfarazi, M .
AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 64 (02) :547-555
[5]   Identification of eight novel VEGFR-3 mutations in families with primary congenital lymphoedema [J].
Evans, AL ;
Bell, R ;
Brice, G ;
Comeglio, P ;
Lipede, C ;
Jeffery, S ;
Mortimer, P ;
Sarfarazi, M ;
Child, AH .
JOURNAL OF MEDICAL GENETICS, 2003, 40 (09) :697-703
[6]   Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome [J].
Fang, JM ;
Dagenais, SL ;
Erickson, RP ;
Arlt, MF ;
Glynn, MW ;
Gorski, JL ;
Seaver, LH ;
Glover, TW .
AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 67 (06) :1382-1388
[7]   Hereditary lymphedema: evidence for linkage and genetic heterogeneity [J].
Ferrell, RE ;
Levinson, KL ;
Esman, JH ;
Kimak, MA ;
Lawrence, EC ;
Barmada, MM ;
Finegold, DN .
HUMAN MOLECULAR GENETICS, 1998, 7 (13) :2073-2078
[8]   Hereditary lymphedema type I associated with VEGFR3 mutation:: the first de novo case and atypical presentations [J].
Ghalamkarpour, A. ;
Morlot, S. ;
Raas-Rothschild, A. ;
Utkus, A. ;
Mulliken, J. B. ;
Boon, L. M. ;
Vikkula, M. .
CLINICAL GENETICS, 2006, 70 (04) :330-335
[9]  
Holberg CJ, 2001, AM J MED GENET, V98, P303, DOI 10.1002/1096-8628(20010201)98:4<303::AID-AJMG1113>3.0.CO
[10]  
2-9