Abstracts
Spinocerebellar ataxia type 10 (SCA10) is a rare form of autosomal dominant ataxia found predominantly in patients from Latin America with Amerindian ancestry. The authors report the history of SCA10 families from the south of Brazil (the states of Paraná and Santa Catarina), emphasizing the Belgian-Amerindian connection.
cerebellar ataxia; spinocerebellar ataxia; SCA10; Amerindians; Belgians; history
A ataxia espinocerebellar tipo 10 (AEC10) é uma forma rara de ataxia cerebelar autossômica dominante, encontrada predominantemente em pacientes da América Latina, de origem Ameríndia. Os autores relatam a história de famílias com AEC10 do sul do Brasil (estados do Paraná e Santa Catarina), enfatizando a conexão Ameríndia-Belga.
ataxia cerebelar; ataxia espinocerebellar; AEC10; ameríndios; belgas; historia
Spinocerebellar ataxia type 10 (SCA10) is a rare form of autosomal dominant cerebellar ataxia
found predominantly in patients from Latin America with Amerindian ancestry11 .Teive HAG, Munhoz RP, Arruda WO, Raskin S, Werneck LC, Ashizawa T.
Spinocerebellar ataxia type 10: a review. Parkinsonism Relat Disord. 2011;17(9): 655-61.
http://dx.doi.org/10.1016/j.parkreldis.2011.04.001
https://doi.org/10.1016/j.parkreldis.201...
. The condition is caused by the expansion of a
non-coding pentanucleotide repeat (ATTCT) within intron 9 of the ataxin 10 (ATXN10) gene on
chromosome 22q13.111 .Teive HAG, Munhoz RP, Arruda WO, Raskin S, Werneck LC, Ashizawa T.
Spinocerebellar ataxia type 10: a review. Parkinsonism Relat Disord. 2011;17(9): 655-61.
http://dx.doi.org/10.1016/j.parkreldis.2011.04.001
https://doi.org/10.1016/j.parkreldis.201...
,22 .Teive HAG, Roa BB, Raskin S, Fang P, Arruda WO, Correa Neto Y. et al.
Clinical phenotype of Brazilian families with spinocerebellar ataxia 10. Neurology.
2004;63(8):1509-12. http://dx.doi.org/10.1212/01.WNL.0000142109.62056.57
https://doi.org/10.1212/01.WNL.000014210...
,33 .Rasmussen A, Matsuura T, Ruano L, Yescas P, Ochoa A, Ashizawa T et al.
Clinical and genetic analysis of four Mexican families with spinocerebellar ataxia type
10. Ann Neurol. 2001;50:234-9. http://dx.doi.org/10.1002/ana.1081
https://doi.org/10.1002/ana.1081...
. SCA10 was originally described in Mexican patients with a clinical
picture characterized by cerebellar ataxia, including gait and limb ataxia, dysarthria and
ocular abnormalities, together with extracerebellar involvement, particularly seizures33 .Rasmussen A, Matsuura T, Ruano L, Yescas P, Ochoa A, Ashizawa T et al.
Clinical and genetic analysis of four Mexican families with spinocerebellar ataxia type
10. Ann Neurol. 2001;50:234-9. http://dx.doi.org/10.1002/ana.1081
https://doi.org/10.1002/ana.1081...
. A study of Mexican patients found that 72.2%
of the study population had epileptic seizures (ranging from 25 to 80%), which presented as
generalized motor seizures and/or complex partial seizures33 .Rasmussen A, Matsuura T, Ruano L, Yescas P, Ochoa A, Ashizawa T et al.
Clinical and genetic analysis of four Mexican families with spinocerebellar ataxia type
10. Ann Neurol. 2001;50:234-9. http://dx.doi.org/10.1002/ana.1081
https://doi.org/10.1002/ana.1081...
. In contrast to these patients, our Brazilian series of SCA10
patients predominantly showed a “pure” cerebellar ataxia, which is in some cases presented
with mild pyramidal signs22 .Teive HAG, Roa BB, Raskin S, Fang P, Arruda WO, Correa Neto Y. et al.
Clinical phenotype of Brazilian families with spinocerebellar ataxia 10. Neurology.
2004;63(8):1509-12. http://dx.doi.org/10.1212/01.WNL.0000142109.62056.57
https://doi.org/10.1212/01.WNL.000014210...
. Another study
confirmed the low frequency of epilepsy (3.75%) in Brazilian SCA10 patients44 .Teive HAG, Munhoz RP, Raskin S, Arruda WO, Paola L, Werneck LC et al.
Spinocerebellar ataxia type 10: frequency of epilepsy in a large sample of Brazilian
patients. Mov Disord. 2010;25(16):2875-8.
http://dx.doi.org/10.1002/mds.23324
https://doi.org/10.1002/mds.23324...
. SCA10 has also been found in patients from
Argentina, Venezuela, Colombia, Bolivia, USA, and, recently, Peru. Like the Mexican SCA10
patients, these patients from Argentina, Venezuela, Colombia, Bolivia, and Peru presented with
epileptic seizures11 .Teive HAG, Munhoz RP, Arruda WO, Raskin S, Werneck LC, Ashizawa T.
Spinocerebellar ataxia type 10: a review. Parkinsonism Relat Disord. 2011;17(9): 655-61.
http://dx.doi.org/10.1016/j.parkreldis.2011.04.001
https://doi.org/10.1016/j.parkreldis.201...
,55 .Leonardi L, Marcotulli C, McFarland KN, Tessa A, DiFabio R, Santorelli FM
et al. Spinocerebellar ataxia type 10 in Peru: the missing link in the Amerindian origin
of the disease. J Neurol. 2014;261(9):1691-4.
http://dx.doi.org/10.1007/s00415-014-7394-8
https://doi.org/10.1007/s00415-014-7394-...
. In 2013, de Castilhos et al. published a study
of SCAs in Brazil, in which they investigated the frequency of the disease and the effect of
modulation by related genes66 .Castilhos RM, Furtado GV, Gheno TC, Schaefer P, Russo A, Barsottini O et
al. Spinocerebellar ataxias in Brazil: frequencies and modulating effects of related
genes. Cerebellum. 2014;13(1):17-28.
http://dx.doi.org/10.1007/s12311-013-0510-y
https://doi.org/10.1007/s12311-013-0510-...
. They studied
544 SCA patients from 359 families in 11 Brazilian cities and found SCA10 in 12 families (3.3%
of the cases). Interestingly, they found that 64.7% of their SCA10 patients exhibited
seizures66 .Castilhos RM, Furtado GV, Gheno TC, Schaefer P, Russo A, Barsottini O et
al. Spinocerebellar ataxias in Brazil: frequencies and modulating effects of related
genes. Cerebellum. 2014;13(1):17-28.
http://dx.doi.org/10.1007/s12311-013-0510-y
https://doi.org/10.1007/s12311-013-0510-...
. Interruptions of the ATTCT
repeat expansions may be a disease modifier that could explain the phenotypic differences
between these SCA10 patients77 .McFarland KN, Liu J, Landrian I, Zeng D, Raskin S, Moscovich M et al.
Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated
with epileptic seizures. Neurogenetics. 2014;15(1):59-64.
http://dx.doi.org/10.1007/s10048-013-0385-6
https://doi.org/10.1007/s10048-013-0385-...
. This
hypothesis is supported by extensive data published by McFarland et al., who concluded that
the presence of repeat interruptions in SCA10 repeat expansions indicates a significant risk
for the epilepsy phenotype77 .McFarland KN, Liu J, Landrian I, Zeng D, Raskin S, Moscovich M et al.
Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated
with epileptic seizures. Neurogenetics. 2014;15(1):59-64.
http://dx.doi.org/10.1007/s10048-013-0385-6
https://doi.org/10.1007/s10048-013-0385-...
. Historically,
several studies support the hypothesis that the ancestors of Amerindians and Native Americans
migrated from eastern central Asia across the exposed Bering land bridge to North America and
then spread to Central and South America55 .Leonardi L, Marcotulli C, McFarland KN, Tessa A, DiFabio R, Santorelli FM
et al. Spinocerebellar ataxia type 10 in Peru: the missing link in the Amerindian origin
of the disease. J Neurol. 2014;261(9):1691-4.
http://dx.doi.org/10.1007/s00415-014-7394-8
https://doi.org/10.1007/s00415-014-7394-...
.
SPINOCEREBELLAR ATAXIA TYPE 10 IN THE SOUTH OF BRAZIL (THE STATES OF PARANÁ AND SANTA CATARINA)
To date, we have studied more than 200 families with SCAs and have found 14 families (90
patients) with SCA type 10 living in the states of Paraná and Santa Catarina (in the south
of Brazil). Of these patients with SCA10, only six (6.6%) presented with epilepsy and
according to their oral history, most of them were of Amerindian descent. Almeida et al.
studied the ancestral origin of the ATTCT repeat expansion in SCA10 and concluded that there
is a common ancestral origin in Latin America for this disease, which may have arisen in an
ancestral Amerindian population and later spread to the mixed population of Mexico, Brazil
and probably other Latin American countries88 .Almeida T, Alonso I, Martins S, Ramos eM, Azevedo L, Ohno K et al.
Ancestral origin of the ATTCT repeat expansion in spinocerebellar ataxia type 10 (SCA10).
PLoS One. 2009;4(2):e4553. http://dx.doi.org/10.1371/journal.pone.0004553
https://doi.org/10.1371/journal.pone.000...
. Our assessment of our series of SCA10 patients, most of whom were
from the state of Santa Catarina, revealed that the families had their origins mainly in the
coastal areas of the state, between the cities of São Francisco do Sul and Florianópolis.
However, the ancestry of 62.5% of the families could be traced back to the town of Ilhota in
the lower Itajaí Valley, state of Santa Catarina. (Figure) In this same area already occupied by Xokleng Indians, were later
populated by European immigrants, such us Belgian, German and also Azorean-Portuguese
immigrants99 .Maes PR. Colonização flamenga em Santa Catarina – Ilhota. Itajaí: Editora
do Autor; 2005.,1010 .Wittmam LT. O vapor e o botoque. Florianópolis: Letras Contemporâneas;
2007..
Santa Catarina State, Ilhota town (red) and historical area of Xokleng´s Indians (blue line).
THE AMERINDIAN-BELGIAN CONNECTION
The town of Ilhota, SC, in the lower Itajaí Valley, has an unusual history as it was the
destination of Belgian immigrants in the 19th century99 .Maes PR. Colonização flamenga em Santa Catarina – Ilhota. Itajaí: Editora
do Autor; 2005.. The Flemish colony in the town of Ilhota in Santa Catarina
was described in a book by Maes published in 200599 .Maes PR. Colonização flamenga em Santa Catarina – Ilhota. Itajaí: Editora
do Autor; 2005.. In 1844 a group of Belgians led by Charles Van Lede immigrated to
Ilhota. A Belgian-Brazilian company was established to operate primarily in mining in the
region between the Itajaí-Açu and Itajaí-Mirim rivers. The “Belgian Colony” experienced
periods of prosperity and failure, with countless quarrels and disagreements between the
settlers, and in 1889 the population stood at four hundred families, one third of whom were
of Belgian descent and the remainder Brazilian99 .Maes PR. Colonização flamenga em Santa Catarina – Ilhota. Itajaí: Editora
do Autor; 2005.. At that time the state of Santa Catarina had a significant
indigenous population, particularly Indians who spoke the Jê language, such as the Xokleng,
or botocudos, as they were better known (Figure). Other indigenous groups
on the Santa Catarina coast included the Tupis-Guaranis (known as the
carijós) and the Kaingang, who were spread along the coast and the Santa
Catarina plateau1010 .Wittmam LT. O vapor e o botoque. Florianópolis: Letras Contemporâneas;
2007.. In the Itajaí Valley
region, between the towns of Ilhota and Blumenau, the main indigenous group was the Xokleng,
who were almost completely wiped out in conflicts with the German population1010 .Wittmam LT. O vapor e o botoque. Florianópolis: Letras Contemporâneas;
2007.. Some descendants of the Xokleng,
particularly females, were sent to Catholic schools to be educated and to learn to read and
write, and others were taken in by families of German descent1010 .Wittmam LT. O vapor e o botoque. Florianópolis: Letras Contemporâneas;
2007.. An example of the latter was the well-known case of the doctor of
German descent, Dr. Hugo Gensch, who adopted the Indian girl Korikrã, who was later to
become “Miss Gensch”1010 .Wittmam LT. O vapor e o botoque. Florianópolis: Letras Contemporâneas;
2007.. Three of the SCA10
families whose origins can be traced to the town of Ilhota each independently confirmed an
interesting story going back to their great-grandfathers, according to which the families’
were descended from an interracial marriage between a Belgian patriarch and a lady of
indigenous descent. After the wife of one of the original settlers in the “Belgian Colony”
in Ilhota died from infection, her widower married his employee, who was of indigenous
origin, and together they had twenty-one children. It is reasonable to suppose that SCA10
spread in the region after these families migrated from the town of Ilhota to neighboring
towns. An interesting question to study is whether this Amerindian/Belgian connection has
any influence on the phenotype observed in most of the SCA10 patients from this region. In
addition, the absence of repeat interruptions in SCA10 repeat expansion might be the cause
of the phenotype of pure cerebellar ataxia without epilepsy77 .McFarland KN, Liu J, Landrian I, Zeng D, Raskin S, Moscovich M et al.
Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated
with epileptic seizures. Neurogenetics. 2014;15(1):59-64.
http://dx.doi.org/10.1007/s10048-013-0385-6
https://doi.org/10.1007/s10048-013-0385-...
.
ACKNOWLEDGMENTS
The authors would like to thank the relatives of the SCA10 families for providing historical information about their families.
References
-
1Teive HAG, Munhoz RP, Arruda WO, Raskin S, Werneck LC, Ashizawa T. Spinocerebellar ataxia type 10: a review. Parkinsonism Relat Disord. 2011;17(9): 655-61. http://dx.doi.org/10.1016/j.parkreldis.2011.04.001
» https://doi.org/10.1016/j.parkreldis.2011.04.001 -
2Teive HAG, Roa BB, Raskin S, Fang P, Arruda WO, Correa Neto Y. et al. Clinical phenotype of Brazilian families with spinocerebellar ataxia 10. Neurology. 2004;63(8):1509-12. http://dx.doi.org/10.1212/01.WNL.0000142109.62056.57
» https://doi.org/10.1212/01.WNL.0000142109.62056.57 -
3Rasmussen A, Matsuura T, Ruano L, Yescas P, Ochoa A, Ashizawa T et al. Clinical and genetic analysis of four Mexican families with spinocerebellar ataxia type 10. Ann Neurol. 2001;50:234-9. http://dx.doi.org/10.1002/ana.1081
» https://doi.org/10.1002/ana.1081 -
4Teive HAG, Munhoz RP, Raskin S, Arruda WO, Paola L, Werneck LC et al. Spinocerebellar ataxia type 10: frequency of epilepsy in a large sample of Brazilian patients. Mov Disord. 2010;25(16):2875-8. http://dx.doi.org/10.1002/mds.23324
» https://doi.org/10.1002/mds.23324 -
5Leonardi L, Marcotulli C, McFarland KN, Tessa A, DiFabio R, Santorelli FM et al. Spinocerebellar ataxia type 10 in Peru: the missing link in the Amerindian origin of the disease. J Neurol. 2014;261(9):1691-4. http://dx.doi.org/10.1007/s00415-014-7394-8
» https://doi.org/10.1007/s00415-014-7394-8 -
6Castilhos RM, Furtado GV, Gheno TC, Schaefer P, Russo A, Barsottini O et al. Spinocerebellar ataxias in Brazil: frequencies and modulating effects of related genes. Cerebellum. 2014;13(1):17-28. http://dx.doi.org/10.1007/s12311-013-0510-y
» https://doi.org/10.1007/s12311-013-0510-y -
7McFarland KN, Liu J, Landrian I, Zeng D, Raskin S, Moscovich M et al. Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures. Neurogenetics. 2014;15(1):59-64. http://dx.doi.org/10.1007/s10048-013-0385-6
» https://doi.org/10.1007/s10048-013-0385-6 -
8Almeida T, Alonso I, Martins S, Ramos eM, Azevedo L, Ohno K et al. Ancestral origin of the ATTCT repeat expansion in spinocerebellar ataxia type 10 (SCA10). PLoS One. 2009;4(2):e4553. http://dx.doi.org/10.1371/journal.pone.0004553
» https://doi.org/10.1371/journal.pone.0004553 -
9Maes PR. Colonização flamenga em Santa Catarina – Ilhota. Itajaí: Editora do Autor; 2005.
-
10Wittmam LT. O vapor e o botoque. Florianópolis: Letras Contemporâneas; 2007.
-
Support: NIH grant NS083564 to Tetsuo Ashizawa.
Publication Dates
-
Publication in this collection
Aug 2015
History
-
Received
14 Dec 2014 -
Reviewed
28 Mar 2015 -
Accepted
16 Apr 2015