Primjer primjene metoda visoke propusnosti: WES u dijagnostici monogenetskih bolesti
Vježba
- U svim zadacima treba pronaci gen uzrocnik urođenog genetskog oboljenja. Dokumnetirati kako ste dosli do tog zakljucka.
- Koji je efekt te mutaije na genskom i proteinskom nivou?
- Koji je slijedeci najbolji kandidat?
- Koji biste dodatni test zatrazili od laboratorija i zasto?
- Koliko je varijanata bilo svaukupno?
- Koji filter je bio najuspjesniji u smanjivanju duljine liste?
- WES analize se mogu naci ovdje.
- Osim ako zadatak ne kaze drugacije, roditelji su asimptomaticni.
- Zadatak 1: A girl with early infantile epileptic encephalopathy (M & V; H nadoknada)
Two sisters, from healthy non-consanguineous parents. Proband: the pregnancy was uneventful, and she was delivered spontaneously with no asphyxia at 39 weeks of gestation. At 3 months of age, she experienced epileptic spasms and electroencephalography (EEG) revealed hypsarrhythmia. At 3 years 2 months, she exhibited focal impaired awareness seizures, which responded well to a combination of clonazepam (CZP) and zonisamide. At 4 years of age, myoclonic seizures appeared and occurred five times per week despite the administration of antiepileptic medications. Her psychomotor development was severely delayed. Her younger sister present similar symptoms with epileptic spasms onset at the age of 4 months.
- Zadatak 2: A boy with neurodevelopmental disorder (T&J)
The boy's family is an extended consanguineous family with three affected childrenin two branches. The parents of each branch are first cousins. The proband, 11-year old boy suffers from delayed development and remains nonverbal and non-ambulatory with profound intellectual disability. During neurologic examination, h e was hypotonic and had dysphagia, muscle weakness and atrophy. Seizures began at age 5. Behaviorally, he show autism, and has demonstrated hand and facial stereotypies, laughing spells, anxiety and mood changes, body rocking, agitation, sleep problems, hyperactivity, bruxism, and hand biting.
- Zadatak 3: A wrinkly woman case (A)
The patient has dry, thin, wrinkled skin, making her look much older than her actual age (33). Subcutaneous fat layer thinned out. Low muscle tone. Hair, nails and teeth normal. Cardiovascular evaluation by echocardiography revealed mitral valve prolapse and diffuse changes in myocardium. Ophthalmologic examination demonstrated exotropia and myopic astigmatism of both eyes. Intelligence normal. No family history of similar conditions.