True about Fragile X syndrome is
Fragile X Syndrome: - * Fragile sites also have a role in tumorigenesis. CGG repeat expansion silences the gene responsible for fragile X mental retardation protein (FMRP) which regulates the translation of multiple mRNA's to specific proteins, hence it affects the synaptic function. * Lack of this FMRP protein upregulates the metabotropic glutamate receptormm pathway. * Lack of FMEP also affects the expression of matrix metalloproteinase Clinical Manifestations in Affected Males are:- * intellectual disability, * autistic behavior, * macroorchidism(may not be evident until pubey) * hyperextensible finger joints, and * characteristic facial features long face, large ears, and a prominent square jaw * Connective tissue abnormalities: mitral valve prolapse, scoliosis, joint laxity, flat feet * Others: seizures (20%), recurrent otitis media (60%), strabismus (8-30%) * Developmental delay- mean IQ = 42 in Males; * IQ is higher if significant residual FMRP is produced (e.g., females and mosaic males or unmethylated full mutations) * Autism 20-30% * ADHD 80% * Anxiety 70-100% Treatment :- * Minocycline (lowers MMP9) has resulted in sho term improvements in anxiety, mood, and the clinical Global Impression Scale. * M-gluR antanogists under trial Ref:- Nelson 20th edition; pg num:- 622,623
Gain of function mutation
Males have IQ 20-40
10% Female carriers are mentally retarded
Triple nucleotide CAG Sequence mutation
Genetic and genetic disorders