Update of PAX2 mutations in renal coloboma syndrome and establishment of a locus-specific database.
Renal coloboma syndrome, also known as papillorenal syndrome is an autosomal-dominant disorder characterized by ocular and renal malformations. Mutations in the paired-box gene, PAX2, have been identified in approximately half of individuals with classic findings of renal hypoplasia/dysplasia and abnormalities of the optic nerve. Prior to 2011, there was no actively maintained locus-specific database (LSDB) cataloguing the extent of genetic variation in the PAX2 gene and phenotypic variation in individuals with renal coloboma syndrome. Review of published cases and the collective diagnostic experience of three laboratories in the United States, France, and New Zealand identified 55 unique mutations in 173 individuals from 86 families. The three clinical laboratories participating in this collaboration contributed 28 novel variations in 68 individuals in 33 families, which represent a 50% increase in the number of variations, patients, and families published in the medical literature. An LSDB was created using the Leiden Open Variation Database platform: www.lovd.nl/PAX2. The most common findings reported in this series were abnormal renal structure or function (92% of individuals), ophthalmological abnormalities (77% of individuals), and hearing loss (7% of individuals). Additional clinical findings and genetic counseling implications are discussed.
Division of Genetics and Metabolism, University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota, USA. mbower1@fairview.org
Matthew
M
Bower
Rémi
R
Salomon
Judith
J
Allanson
Corinne
C
Antignac
Francesco
F
Benedicenti
Elisa
E
Benetti
Gil
G
Binenbaum
Uffe B
UB
Jensen
Pierre
P
Cochat
Stephane
S
DeCramer
Joanne
J
Dixon
Regen
R
Drouin
Marni J
MJ
Falk
Holly
H
Feret
Robert
R
Gise
Alasdair
A
Hunter
Kisha
K
Johnson
Rajiv
R
Kumar
Marie Pierre
MP
Lavocat
Laura
L
Martin
Vincent
V
Morinière
David
D
Mowat
Luisa
L
Murer
Hiep T
HT
Nguyen
Gabriela
G
Peretz-Amit
Eric
E
Pierce
Emily
E
Place
Nancy
N
Rodig
Ann
A
Salerno
Sujatha
S
Sastry
Tadashi
T
Sato
John A
JA
Sayer
Gerard C P
GC
Schaafsma
Lawrence
L
Shoemaker
David W
DW
Stockton
Wen-Hann
WH
Tan
Romano
R
Tenconi
Philippe
P
Vanhille
Abhay
A
Vats
Xinjing
X
Wang
Berta
B
Warman
Richard G
RG
Weleber
Susan M
SM
White
Carolyn
C
Wilson-Brackett
Dina J
DJ
Zand
Michael
M
Eccles
Lisa A
LA
Schimmenti
Laurence
L
Heidet
D000818:Animals; D003103:Coloboma / Q000235:genetics*; D030541:Databases, Genetic; D006801:Humans; D051762:PAX2 Transcription Factor / Q000235:genetics*; D051437:Renal Insufficiency / Q000235:genetics*; D014718:Vesico-Ureteral Reflux / Q000235:genetics*
D051762:PAX2 Transcription Factor