Clinical Features and Molecular Genetics of Hereditary 遗传性的临床特点和分子遗传学.ppt

Autosomal Dominant Ataxia Evaluation #680 Type of Disorder: Movement Disorders Typical Presentation: Ataxia, poor coordination of hand, speech and eye movements, uncoordinated and unsteady gait Disease(s) tested for:SCA1, SCA2, SCA3 (MJD), SCA5, SCA6, SCA7, SCA8, SCA10, SCA13, SCA14, SCA17 DRPLA DRPLA DNA Test, SCA1 DNA Test, SCA10 DNA Test, SCA13 Select Exon DNA Test, SCA14 DNA Test, SCA17 DNA Test, SCA2 DNA Test, SCA3 (Machado-Joseph Disease) DNA Test, SCA5 Select Exon DNA Test, SCA6 DNA Test, SCA7 DNA Test, SCA8 DNA Test Genetic Testing (Athena Diagnostics) Frequency of SCA types SCA3 is the most common (30-40%) AKA: Machado-Joseph Disease In the US most common in East Coast, NE, Rhode Island, Maryland, NC and in West Coast (CA), migration of Portuguese immigrants SCA2 accounts for ~15-20% SCA1 accounts for ~10% Note: OPCA (MRI shows pontocerebellar atrophy) is associated with SCA1 and 2 SCA10, epilepsy PATIENT 2 53 year-old gentleman with 10 year-history of progressive problems with balance Normal development, was very athletic First symptom was ataxia of gait Followed by slurring of speech Urinary urgency and cramps Family History: Positive for cerebellar ataxia in 5 of his 7 siblings and in his mother deceased at 72. Earlier onset of disease in sibs (~35) and different severity of disease. DNA testing: SCA2 PATIENT 1 47 year-old gentleman with 7-8 year-history of progressive problems with balance Normal development, was very athletic First symptom was slurring of speech Followed by ataxia of gait No sensory, memory, visual, sphincter deficits Family History: negative, parents still alive, mother may have mild dementia. No history of consanguinity. Blood tests prior to his visit: gliadin and tissue trans-glutaminase antibodies were negative. Transaminase, vitamin E, sed rate, ANA, Lyme titer, TSH, SSA, SSB, methylmalonic acid, homocysteine within normal limits. DNA testing: SCA8 Copyright restrictions may apply. Nemes, J. P. et al. Hum. Mol.