High-risk fragile x screening in Guatemala: use of a new blood spot polymerase chain reaction technique.
BACKGROUND
Because fragile X syndrome (FXS) is prevalent, it has become the subject of newborn and high-risk screening efforts. International screening, however, can be financially and logistically prohibitive, particularly in countries where resources may be scarce. Recently, we have developed a screening test on blood spot that can detect expanded alleles from the normal through the full mutation range in both males and females. It is accurate, rapid, inexpensive, and applicable on blood spots and therefore ideal for international screening. The use of this blood spot screening technique was piloted in "a high-risk screening" study of individuals in Guatemala.


METHODS
One hundred and five blood spots from subjects from Guatemala were screened for the Fragile X Mental Retardation 1 mutation. They were classified as "high-risk" through placement into one of the following five categories: (a) relatives of someone with a previous FXS diagnosis, (b) individuals with confirmed autism, (c) individuals with confirmed intellectual disability, (d) individuals with Parkinson's-like presentation, and (e) individuals with a family history of intellectual disability but no confirmed cases of FXS.


RESULTS
Fifteen of the individuals tested yielded an expanded allele, 10 premutations and 5 full mutations. All 15 expansions were found in individuals with a relative with a confirmed FXS diagnosis. No expansions were found in the other clinical groups.


CONCLUSIONS
Blood spot polymerase chain reaction screening is an effective, cost-efficient method to conduct cascade testing in families with a known history of FXS, even in small screening cohorts.
Yuhas
Jennifer
J
M.I.N.D. Institute, University of California Davis Medical Center, Sacramento, California, USA.
Walichiewicz
Paulina
P
Pan
Ruiqin
R
Zhang
Wenting
W
Casillas
E Melina
EM
Hagerman
Randi J
RJ
Tassone
Flora
F
D000328:Adult; D003362:Cost-Benefit Analysis; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000097:blood / Q000175:diagnosis*; D005820:Genetic Testing / Q000379:methods*; D006166:Guatemala; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000191:economics / Q000379:methods*; D012306:Risk
D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human