Chapter 6: Clinical Genetics Flashcards
What are methods of identifying carrier heterozygotes?
- Electrophoresos (ID’ing abnormal metabolites)
- hair bulb assay
- Skin Cx (analysis of enzyme activity in fibroblasts)
- Assay of serum and tears
What percentage of patients with RP have no family history?
40-50%
What do AD inherited defects often represent?
They typically represent non-enzymatic structural proteins
What constitutes conclusive evidence of an AD diease?
Demonstration of the disease in three successive generations
male to male transmission must also occur
What is a key feature of an X Linked disease pedigree?
No male to male transmission
What are the different patterns of inheritence for RP?
AR, AD, X-Linked recessive, and mitochondrial–all of which occur via different genetic defects
In a pregnant mother, what does a chromosomally abnormal state in a previous child warrant?
Either CVS or Amniocentesis
What are the ocular findings in Down Syndrome?
- almond shaped or upslanting palpebral fissures
- prominent epicanthal folds
- blepharitis (typically chronic) with cicatricial ectropion
- nasolacrimal duct obstruction
- strabismus (usually esotropic)
- nystagmus (usually horizontal)
- aberrant retinal vessels (disc)
- Iris stromal hypoplasia
- Brushfield Spots
- Keratoconus
- Cataracts
- Myopia
- Optic Atrophy
What is the long arm 13 deletion?
the deletion of the long arm of chromosome 13 (13q14) is a genetic cause of retinoblastoma
It exhibits both hereditary occurrance (30-40%, where tumors tend to be bilateral and multicentric) and sporadic (unilateral and solitary)
For the 13q14 deletion (long arm), what percentage of mutations will have a karyotypically visible deletion? And what is an indicator of a more severe syndrome?
3-7% of all cases have a karyotypically visible deletion
The larger the deletion, the more severe the syndrome
What does the short arm 11 deletion (11p13) syndrome cause?
Aniridia
What are the symptoms of short arm 11 deletion?
- subnormal VA
- congenital nystagmus
- strabismus
- keratitis 2/2 limbal stem cell failure
- cataracts (usually anterior pole)
- ectropia lentis
- glaucoma
- ON hypoplasia
- foveal or macular hypoplasia
- iris absence or severe hypoplasia
What are other causes of Aniridia?
- Short Arm 11 syndrome
- Gillespie Syndrome (= rare AR disorder that produces partial aniridia, cerbellar ataxia, mental deficiency, and congenital cataracts)
- WAGR syndrome
What is haploinsufficiency? What is an example that is related to ophthalmology?
Haploinsuffiency is the inability of a single active allele to activate transduction or the developmental genes regualted by PAX 6 gene product
PAX6 mutation
What is the population risk for developing primary open angle glaucoma?
2-3%
