Professional Documents
Culture Documents
Uk Fragile X
Uk Fragile X
Uk Fragile X
Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow,
India. Email: [email protected]
Abstract
Key words
History
Etiology
Prevalence of fragile X syndrome
Clinical features
Diagnosis
Management
Genetics of Fragile X syndrome:
Genetic Counseling
Prenatal diagnosis
Reference
Abstract
Fragile X syndrome is the most frequent cause of inherited mental retardation. It is caused by a dynamic
mutation i.e. the progressive expansion of polymeric (CGG)n trinucleotide repeats located in the non
coding region at the 5 end of the FMR1 gene at Xq 27.3. It is an X linked disorder; the manifestations are
seen in all of carrier males and in 35% of carrier females. This type of mode of inheritance is described as
X linked semidominant or X linked dominant with decreased penetrance. The clinical features other than
mental retardation include subtle dysmorphism, behavioral abnormalities and macroorchidism in
postpubertal males. The phenotype being subtle, clinical diagnosis may be difficult especially in young
children. Hence, all cases of mental retardation without obvious cause should be tested for fragile X
syndrome, it is often the only way to identify fragile X syndrome cases. The parents and relatives of such
a case need to be offered genetic counseling to prevent the recurrence of fragile X syndrome in the
family. The cytogenetic and molecular diagnostic tests are available; the latter replacing the formers over
the years. Polymerase chain reaction based tests are used for screening and Southern blot hybridization
is the diagnostic test for detections of mutation and premutation. Prenatal diagnosis is possible by
carrying out Southern blot hybridization on samples of chorionic villi or amniotic fluid. The complexities
due to premutation and variable severity of manifestations in carrier females need to be understood while
counseling families with fragile X syndrome.
Key words
Fragile X syndrome, mutations, premutations, X linked semidominant, mental retardation, trinucleotide
repeat disorder, dynamic mutation, genetic counseling.