Possible anticipation associated with a novel splice site mutation in episodic ataxia type 2

Choi, Kwang-Dong; Yook, Ji-Won; Kim, Min-Ji; Kim, Hyang-Sook; Park, Young-Eun; Kim, Ji; Choi, Jae-Hwan; Shin, Jin-Hong; Kim, Dae-Seong
September 2013
Neurological Sciences;Sep2013, Vol. 34 Issue 9, p1629
Academic Journal
Anticipation is a phenomenon characterized by decreasing age at onset and increasing severity of symptoms of a disease in successive generations within a pedigree. Anticipation mostly occurs in neurodegenerative diseases with expansion of unstable trinucleotide repeats. However, it has not been previously pointed out in episodic ataxia type 2 (EA2). Clinical and genetic analyses were performed in nine members from three consecutive generations of a Korean family with EA2. We performed a polymerase chain reaction (PCR)-based direct sequence analysis of all coding regions of CACNA1A using genomic DNA. The clinically affected family members showed recurrent vertigo, interictal nystagmus, and childhood epilepsy. There is a decrease in the age onset (possible genetic anticipation) in three succeeding generations of the family. Genetic analysis identified a splice site mutation (p.Val1465Glyfs13X) and normal trinucleotide repeats in CACNA1A in all clinically affected and one unaffected members. Recognizing anticipation would aid in genetic counseling in EA2.


Related Articles

  • Fluorescent Multiplex PCR: Fast Method for Autosomal Dominant Spinocerebellar Ataxias Screening. Bauer, P. O.; Kotliarova, S. E.; Matoška, V.; Musova, Z.; Hedvicakova, P.; Boday, A.; Tomek, A.; Nukina, N.; Goetz, P. // Russian Journal of Genetics;Jun2005, Vol. 41 Issue 6, p675 

    Expansion of CAG trinucleotide repeats has been shown to cause a number of autosomal dominant spinocerebellar ataxias such as SCA1, SCA2, SCA3/MJD, SCA6, and SCA7. These disorders are characterized by a wide inter- and intrafamiliar variation in clinical features. The same mutation can result in...

  • Rescue of the Friedreich Ataxia Knockout Mutation in Transgenic Mice Containing an FXN-EGFP Genomic Reporter. Sarsero, Joseph P.; Holloway, Timothy P.; Li, Lingli; Finkelstein, David I.; Ioannou, Panos A. // PLoS ONE;Mar2014, Vol. 9 Issue 3, p1 

    Friedreich ataxia (FRDA) is an autosomal recessive disorder characterized by neurodegeneration and cardiomyopathy. The presence of a GAA trinucleotide repeat expansion in the first intron of the FXN gene results in the inhibition of gene expression and an insufficiency of the mitochondrial...

  • Typical Friedreich's ataxia without GAA expansions and GAA expansions without typical Friedreich's ataxia. McCabe, D.J.H.; Ryan, F.; Moore, D.P.; McQuaid, S.; King, M.D.; Kelly, A.; Daly, K.; Barton, D.E.; Murphy, R.P. // Journal of Neurology;May2000, Vol. 247 Issue 5, p346 

    We clinically assessed and performed polymerase chain reaction analysis for the GAA trinucleotide repeat expansion in 103 patients from 73 families in Ireland, with a prior clinical diagnosis of Friedreich's ataxia (FA) or an unclassified progressive ataxic syndrome. The patients were classified...

  • Instability of expanded CAG/CAA repeats in spinocerebellar ataxia type 17. Gao, Rui; Matsuura, Tohru; Coolbaugh, Mary; Zühlke, Christine; Nakamura, Koichiro; Rasmussen, Astrid; Siciliano, Michael J.; Ashizawa, Tetsuo; Lin, Xi // European Journal of Human Genetics;Feb2008, Vol. 16 Issue 2, p215 

    Trinucleotide repeat expansions are dynamic mutations causing many neurological disorders, and their instability is influenced by multiple factors. Repeat configuration seems particularly important, and pure repeats are thought to be more unstable than interrupted repeats. But direct evidence is...

  • Spinocerebellar ataxia type 11 in the Chinese Han population. Qian Xu; Xiaohui Li; Junling Wang; JiPing Yi; Lifang Lei; Lu Shen; Hong Jiang; Kun Xia; Qian Pan; Beisha Tang // Neurological Sciences;Feb2010, Vol. 31 Issue 1, p107 

    The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative diseases. Researchers have recently found that SCA type 11 (SCA11) is associated with mutations in the TTBK2 gene. In our previous work, we performed mutation detection in SCA1, 2, 3, 6,...

  • Trinucleotide repeat spinocerebellar ataxias: experience of a tertiary care centre in Western India with review of Indian literature. Khadilkar, Satish V.; Dabi, Rajesh; Dhonde, Pramod; Nadkarni, Nilesh; Kulkarni, Smita; Sarnath, Dhananjaya // Neurology Asia;Sep2012, Vol. 17 Issue 3, p213 

    Consecutive index cases with trinucleotide repeat spinocerebellar ataxia (SCA) presenting from August 2006 to August 2008 to a tertiary care university department were studied clinically, radiologically and genetically (repeat expansions at SCA 1, 2, 3, 6, 7, 10 and 12). CAG repeat expansions...

  • Diagnosis and Genetic Counseling for Friedreich's Ataxia: A time for consideration of TP-PCR in an Indian Setup. Muthuswamy, S.; Agarwal, S.; Dalal, A. R. // Hippokratia;2013, Vol. 17 Issue 1, p38 

    Background and Introduction: Expansion of GAA triplet repeats in the first intron of the frataxin gene causes Friedreich's ataxia. Genetic testing in such condition is important to initiate the appropriate genetic counseling for the family members. The conventional genetic tests used in the...

  • A study of six point mutation analysis of LRRK2 gene in Chinese mainland patients with Parkinson's disease. Hu, Z.; Peng, D.; Cai, M.; Pu, J.; Lei, X.; Yin, X.; Ou-Yang, Z.; Luo, W.; Zhang, B. // Neurological Sciences;Aug2011, Vol. 32 Issue 4, p741 

    No abstract available.

  • Spinocerebellar Ataxia Type 2 (SCA2): Clinical Features and Genetic Analysis. Léon Mutesa; Geneviève Pierquin; Karin Segers; Jean François Vanbellinghen; Laetitia Gahimbare; Vincent Bours // Journal of Tropical Pediatrics;Oct2008, Vol. 54 Issue 5, p350 

    Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease that results from the expansion of an unstable trinucleotide CAG repeat encoding for a polyglutamine tract. In normal individuals, alleles contain between 14 and 31 CAG repeats, whereas the pathological...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics