Repeat Offenders
Expansion of more than ~200 CGG repeats leads to abnormal methylation and gene silencing
What is FXS?
This inherited cardiomyopathy is the most common cause of sudden cardiac death in athletes
What is hypertrophic cardiomyopathy?
Repeat expansion, most commonly increases during this process leading to anticipation and Huntington's disease
What is spermatogenesis?
UPD, CNV, SNV, and epigenetic defects represent four mechanisms affecting this parent-of-origin dependent process
What is genomic imprinting?
My repeats expand upon the X,
Past a limit gene defects,
Methyl marks will shut me down,
Leading to a learning frown.
What is fragile X syndrome?
Sequence interruptions within the CGG repeat tract reduce the likelihood of repeat expansions during transmission
What are AGG interruptions?
Genetic testing yield for this condition increases from about 40% to about 60% when this factor is present
What is a positive family history?
More than 90% of juvenile-onset Huntington disease cases inherit the expanded allele from this parent
Who is the father?
Loss of paternal gene expression on chromosome 15 results in this imprinting disorder
What is Prader-Willi syndrome?
From father I often grow,
Generation makes me show,
Testing rules must guide the way,
Before results are given, one day.
What is Huntington disease?
This repeat expansion disorder is caused by repeats in intron one, is usually biallelic, and typically does not demonstrate anticipation because of its inheritance pattern
What is Friedreich ataxia?
Variance in these two sarcomeric genes account for many familial cases of hypertrophic cardiomyopathy
What are MYH7 and MYBPC3?
Patients pursuing predictive testing for Huntington disease must be:
Voluntary, informed, emotionally safe, and confidential
Imprinting defects involving growth, regulating genes on chromosome 11p15.5 or chromosome seven are associated with the syndrome
What is Russell-Silver syndrome?
The heart appears completely fine,
Yet rhythm fails without a sign,
Triggers vary, genes decide,
Sudden death may still reside.
What is long QT syndrome?
This combination of molecular techniques is considered the gold standard for detecting expansions in fragile X syndrome
What are Southern blot and PCR?
In this arrhythmia syndrome, cardiac arrest may be the first sign and up to 30% of affected individuals can have a normal QT interval
What is Long QT syndrome?
The predictive testing protocol includes four steps beginning with this initial form of contact
What is the initial phone call?
A neurodevelopmental disorder results when the maternal allele on chromosome 15 is nonfunctional due to deletion, mutation or imprinting defect producing severe speech, impairment, ataxia, and a happy demeanor, despite normal karyotype
What is Angelman syndrome?
Large at birth with tongue so wide,
One side grows more than the other side,
Chromosome 11 marks the theme,
With methyl loss behind the scene
What is Beckwith-Wiedemann syndrome?
This term describes repeat sizes that fall between clearly normal and fully penetrant disease alleles, such as 44 to 65 repeats in Friedrich ataxia where risk is uncertain
What is borderline or intermediate repeat range?
Gain a function variance in the sodium channel gene cause LQTS3, while loss of function variance can cause Brugada syndrome
What is SCN5A?
After visit one and the in person disclosure, this final step is required as part of the recommended Huntington disease testing process
What is post test follow up?
Overgrowth, organomegaly and predisposition to embryonal tumors can arise from abnormal methylation or copy number changes on this chromosome, often requiring molecular analysis of imprinting centers to confirm
What is chromosome 11p15.5?
I do not strike twice in every line,
One generation shows my sign,
My repeats expand yet stay concealed,
Because recessive genes are sealed
What is Friedrich ataxia?