Genetics Myotonic dystrophy

myotonic dystrophy inherited in autosomal dominant pattern.

myotonic dystrophy genetic condition inherited in autosomal dominant pattern , passed along 50% of carrier s offspring, on average. myotonic dystrophy 1 of several known trinucleotide repeat disorders. areas of dna have repeated sequences of 2 or 3 nucleotides.

myotonic dystrophy (dm) inherited disease. severe form of dm, congenital myotonic dystrophy, may appear in newborns of mothers have dm. congenital myotonic dystrophy can inherited via paternal gene, although said relatively rare. congenital means condition present birth.

dm1

in dm1, affected gene called dmpk, codes myotonic dystrophy protein kinase, protein expressed predominantly in skeletal muscle. gene located on long arm of chromosome 19.

histopathology of dm2. muscle biopsy showing mild myopathic changes , grouping of atrophic fast fibres (type 2, highlighted). immunohistochemical staining type-1 ( slow ) myosin

in dm1, there expansion of cytosine-thymine-guanine (ctg) triplet repeat in dmpk gene. between 5 , 37 repeats considered normal, while individuals between 38 , 49 repeats considered have pre-mutation , @ risk of having children further expanded repeats and, therefore, symptomatic disease. individuals greater 50 repeats invariably symptomatic, noted exceptions. longer repeats associated earlier onset , more severe disease.

dmpk alleles greater 37 repeats unstable , additional trinucleotide repeats may inserted during cell division in mitosis , meiosis. consequently, children of individuals premutations or mutations inherit dmpk alleles longer parents , therefore more affected or display earlier onset , greater severity of condition, phenomenon known anticipation. interestingly, paternal transmission of condition uncommon, possibly due selection pressures against sperm expanded repeats, anticipation tends less severe in cases of maternal inheritance.

the rna expanded trinucleotide repeat region forms intranucleoplasmic hairpin loops due extensive hydrogen bonding between c-g base pairs, , has been demonstrated these sequester splicing regulator mbnl1 form distinctive foci labelling gfp , probe oligonucleotide red-fluorescent dye cyanine5 (cy5)

dm2

dm2 caused defect of cnbp gene on chromosome 3. specific defect repeat of cytosine-cytosine-thymine-guanosine (cctg) tetranucleotide in cnbp gene. involves repeat of 4 nucleotides, not trinucleotide repeat disorder, rather tetranucleotide repeat disorder.

the repeat expansion dm2 larger dm1, ranging 75 on 11,000 repeats. unlike in dm1, size of repeated dna expansion in dm2 not appear make difference in age of onset or disease severity. anticipation appears less significant in dm2 , current reviews report mild anticipation feature of dm2.