Consensus characterization of 16 FMR1 reference materials: a consortium study.
Fragile X syndrome, which is caused by expansion of a (CGG)(n) repeat in the FMR1 gene, occurs in approximately 1:3500 males and causes mental retardation/behavioral problems. Smaller (CGG)(n) repeat expansions in FMR1, premutations, are associated with premature ovarian failure and fragile X-associated tremor/ataxia syndrome. An FMR1-sizing assay is technically challenging because of high GC content of the (CGG)(n) repeat, the size limitations of conventional PCR, and a lack of reference materials available for test development/validation and routine quality control. The Centers for Disease Control and Prevention and the Association for Molecular Pathology, together with the genetic testing community, have addressed the need for characterized fragile X mutation reference materials by developing characterized DNA samples from 16 cell lines with repeat lengths representing important phenotypic classes and diagnostic cutoffs. The alleles in these materials were characterized by consensus analysis in nine clinical laboratories. The information generated from this study is available on the Centers for Disease Control and Prevention and Coriell Cell Repositories websites. DNA purified from these cell lines is available to the genetics community through the Coriell Cell Repositories. The public availability of these reference materials should help support accurate clinical fragile X syndrome testing.
Amos Wilson
Jean
J
Sequenom, San Diego, California, USA.
Pratt
Victoria M
VM
Phansalkar
Amit
A
Muralidharan
Kasinathan
K
Highsmith
W Edward
WE
Beck
Jeanne C
JC
Bridgeman
Scott
S
Courtney
Ebony M
EM
Epp
Lidia
L
Ferreira-Gonzalez
Andrea
A
Hjelm
Nick L
NL
Holtegaard
Leonard M
LM
Jama
Mohamed A
MA
Jakupciak
John P
JP
Johnson
Monique A
MA
Labrousse
Paul
P
Lyon
Elaine
E
Prior
Thomas W
TW
Richards
C Sue
CS
Richie
Kristy L
KL
Roa
Benjamin B
BB
Rohlfs
Elizabeth M
EM
Sellers
Tina
T
Sherman
Stephanie L
SL
Siegrist
Karen A
KA
Silverman
Lawrence M
LM
Wiszniewska
Joanna
J
Kalman
Lisa V
LV
D000483:Alleles; D001483:Base Sequence; D001681:Biological Assay; D015139:Blotting, Southern; D002460:Cell Line; D032921:Consensus; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D012015:Reference Standards; D017422:Sequence Analysis, DNA; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human