Testing for genetic forms of developmental abnormalities Flashcards
development disorders can be on a phenotypic spectrum and can be syndromic or non-syndromic
problems can be categorised as …
abnormal growth - of body or specific parts
deformities (birth defects) such as cleft lip or extra digits
intellectually disability - problems with learning and behaviour
major classes of inheritance fro genetic conditions
autosomal dominant ( inherited or spontaneous mutation so only present in the child)
autosomal recessive forms - both copies - generally inherited , each parent are carriers
X linked conditions - present differently with boys and girls - particularly prevent in boys inherited from carrier mother
major classes of genetic mutations
single nucleotide variant SNV - one base change
insertions or deletions ( indwells)
copy number variants CMVs - 100s bases duplicated or deleted - large
chromosomal aneuploidies - trisonmys and monosomy like turners
what genomic tests available
light microscope - entire chromosome detects aneuploidy lowest diagosnotic yeild - condense great for anueploidys
g-banded karyotype - 5-10Mb higher resolution see about 500 loci and most cases won’t detect - entire chromosomal and recognise specific loci
DNA microarray - 1st line for developmental disorders in children - copy number variant changes - specific suspected deletion or insertion - good for picking up
whole-exome - sequence - coding regions - cell samples
whole-genome sequence - majority of variants
difference between syndromic and non-syndromic
e.g. Nonsyndromic deafness is hearing loss that is not associated with other signs and symptoms. means no abnromltiy associated with it
In contrast, syndromic deafness involves hearing loss that occurs with abnormalities in other parts of the body. e.g. short stature, webbed neck , prepubescent is indicative of turners syndrome
difference between screening tests and diagnostic tests
Screening tests evaluate an individual’s risk of developing a genetic condition, while diagnostic tests identify genetic conditions.
karyotyping is easy to visualise aneuploidy and large changes but is reliant on the sample and and could miss suble changes why is microarray good and bad
chepa and does not need microscope however limited info, only specific pathologies are tests and cannot identify balanced structural changes or mosaicism
exome sequencing analyse lots of genes for SNVs and CNVs but expensive and miss introns and a good sample is required.
what about whole genome sequencing
analysis whole genome and has a high diagnostic rate. however expensive and mtutuaion son unknown or no significance are not found
antenatal screening
offered to all parties and must be complete before 23 weeks
combined test includes what
10-14 weeks combined test
blood tests include pregnancy associated plasma protein A(PAPP-A) and free human beta HCG
USS scan for nuchal translucency
maternal age - quadruple test offered if NT measurement cannot be advised or if presenting too late for combined - performed at 14-20 weeks
20 week screening pathway
18 -20+6 weeks USS
screen fro 11 disease
newborn baby with failure to thrive what test and treatment
genome test and immediate treatment of cobalamin fro transcobalamin II deficiency
what is a Robertson’s translocation
A Robertsonian translocation is one in which, effectively, the whole of a chromosome is joined end to end with another. This type of translocation involves only chromosomes 13, 14, 15, 21 and 22, because the ends of their short arms have similar repetitive DNA sequences that predispose to their fusion.
this allows to extra chromosome
