Genetic Analysis of Hereditary Ataxias in Peru Identifies SCA10 Families with Incomplete Penetrance

on behalf of Rede Neurogenetica

doi:10.1007/s12311-019-01098-2

Genetic Analysis of Hereditary Ataxias in Peru Identifies SCA10 Families with Incomplete Penetrance

on behalf of Rede Neurogenetica

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Relative frequency of hereditary ataxias remains unknown in many regions of Latin America. We described the relative frequency in spinocerebellar ataxias (SCA) due to (CAG)n and to (ATTCT)n expansions, as well as Friedreich ataxia (FRDA), among cases series of ataxic individuals from Peru. Among ataxic index cases from 104 families (38 of them with and 66 without autosomal dominant pattern of inheritance), we identified 22 SCA10, 8 SCA2, 3 SCA6, 2 SCA3, 2 SCA7, 1 SCA1, and 9 FRDA cases (or families). SCA10 was by far the most frequent one. Findings in SCA10 and FRDA families were of note. Affected genitors were not detected in 7 out of 22 SCA10 nuclear families; then overall maximal penetrance of SCA10 was estimated as 85%; in multiplex families, penetrance was 94%. Two out of nine FRDA cases carried only one allele with a GAA expansion. SCA10 was the most frequent hereditary ataxia in Peru. Our data suggested that ATTCT expansions at ATXN10 might not be fully penetrant and/or instability between generations might frequently cross the limits between non-penetrant and penetrant lengths. A unique distribution of inherited ataxias in Peru requires specific screening panels, considering SCA10 as first line of local diagnosis guidelines.

Original language	English
Pages (from-to)	208-215
Number of pages	8
Journal	Cerebellum
Volume	19
Issue number	2
DOIs	https://doi.org/10.1007/s12311-019-01098-2
State	Published - 1 Apr 2020

Bibliographical note

Funding Information:
EPM, GVF, GBB, SLS, MLSP, and LBJ were supported by the National Council for Research and Development (CNPq), Brazil. LBJ received grants from Fundo de Incentivo à Pesquisa do Hospital de Clínicas de Porto Alegre (FIPE 2006-0384) and Pesquisa para o SUS/Fundo de Apoio à Pesquisa do Rio Grande do Sul, Brazil (PPSUS-FAPERGS, PROCESS 07-00832), for performing the laboratory procedures. MCO, MIM, VM, and PM are partially supported by research funds provided by Instituto Nacional de Ciencias Neurológicas. Acknowledgments

Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

CAG repeats
Friedreich ataxia
Inherited ataxias
Penetrance
Peru
Spinocerebellar ataxia

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10.1007/s12311-019-01098-2

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title = "Genetic Analysis of Hereditary Ataxias in Peru Identifies SCA10 Families with Incomplete Penetrance",

abstract = "Relative frequency of hereditary ataxias remains unknown in many regions of Latin America. We described the relative frequency in spinocerebellar ataxias (SCA) due to (CAG)n and to (ATTCT)n expansions, as well as Friedreich ataxia (FRDA), among cases series of ataxic individuals from Peru. Among ataxic index cases from 104 families (38 of them with and 66 without autosomal dominant pattern of inheritance), we identified 22 SCA10, 8 SCA2, 3 SCA6, 2 SCA3, 2 SCA7, 1 SCA1, and 9 FRDA cases (or families). SCA10 was by far the most frequent one. Findings in SCA10 and FRDA families were of note. Affected genitors were not detected in 7 out of 22 SCA10 nuclear families; then overall maximal penetrance of SCA10 was estimated as 85%; in multiplex families, penetrance was 94%. Two out of nine FRDA cases carried only one allele with a GAA expansion. SCA10 was the most frequent hereditary ataxia in Peru. Our data suggested that ATTCT expansions at ATXN10 might not be fully penetrant and/or instability between generations might frequently cross the limits between non-penetrant and penetrant lengths. A unique distribution of inherited ataxias in Peru requires specific screening panels, considering SCA10 as first line of local diagnosis guidelines.",

keywords = "CAG repeats, Friedreich ataxia, Inherited ataxias, Penetrance, Peru, Spinocerebellar ataxia",

author = "{on behalf of Rede Neurogenetica} and Mario Cornejo-Olivas and Miguel Inca-Martinez and Castilhos, {Raphael Machado} and Furtado, {Gabriel Vasata} and Mattos, {Eduardo Preusser} and Bampi, {Giovana Bavia} and Sandra Leistner-Segal and Victoria Marca and Pilar Mazzetti and Saraiva-Pereira, {Maria Luiza} and Jardim, {Laura Bannach}",

note = "Publisher Copyright: {\textcopyright} 2020, Springer Science+Business Media, LLC, part of Springer Nature.",

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T1 - Genetic Analysis of Hereditary Ataxias in Peru Identifies SCA10 Families with Incomplete Penetrance

AU - on behalf of Rede Neurogenetica

AU - Cornejo-Olivas, Mario

AU - Inca-Martinez, Miguel

AU - Castilhos, Raphael Machado

AU - Furtado, Gabriel Vasata

AU - Mattos, Eduardo Preusser

AU - Bampi, Giovana Bavia

AU - Leistner-Segal, Sandra

AU - Marca, Victoria

AU - Mazzetti, Pilar

AU - Saraiva-Pereira, Maria Luiza

AU - Jardim, Laura Bannach

PY - 2020/4/1

Y1 - 2020/4/1

N2 - Relative frequency of hereditary ataxias remains unknown in many regions of Latin America. We described the relative frequency in spinocerebellar ataxias (SCA) due to (CAG)n and to (ATTCT)n expansions, as well as Friedreich ataxia (FRDA), among cases series of ataxic individuals from Peru. Among ataxic index cases from 104 families (38 of them with and 66 without autosomal dominant pattern of inheritance), we identified 22 SCA10, 8 SCA2, 3 SCA6, 2 SCA3, 2 SCA7, 1 SCA1, and 9 FRDA cases (or families). SCA10 was by far the most frequent one. Findings in SCA10 and FRDA families were of note. Affected genitors were not detected in 7 out of 22 SCA10 nuclear families; then overall maximal penetrance of SCA10 was estimated as 85%; in multiplex families, penetrance was 94%. Two out of nine FRDA cases carried only one allele with a GAA expansion. SCA10 was the most frequent hereditary ataxia in Peru. Our data suggested that ATTCT expansions at ATXN10 might not be fully penetrant and/or instability between generations might frequently cross the limits between non-penetrant and penetrant lengths. A unique distribution of inherited ataxias in Peru requires specific screening panels, considering SCA10 as first line of local diagnosis guidelines.

AB - Relative frequency of hereditary ataxias remains unknown in many regions of Latin America. We described the relative frequency in spinocerebellar ataxias (SCA) due to (CAG)n and to (ATTCT)n expansions, as well as Friedreich ataxia (FRDA), among cases series of ataxic individuals from Peru. Among ataxic index cases from 104 families (38 of them with and 66 without autosomal dominant pattern of inheritance), we identified 22 SCA10, 8 SCA2, 3 SCA6, 2 SCA3, 2 SCA7, 1 SCA1, and 9 FRDA cases (or families). SCA10 was by far the most frequent one. Findings in SCA10 and FRDA families were of note. Affected genitors were not detected in 7 out of 22 SCA10 nuclear families; then overall maximal penetrance of SCA10 was estimated as 85%; in multiplex families, penetrance was 94%. Two out of nine FRDA cases carried only one allele with a GAA expansion. SCA10 was the most frequent hereditary ataxia in Peru. Our data suggested that ATTCT expansions at ATXN10 might not be fully penetrant and/or instability between generations might frequently cross the limits between non-penetrant and penetrant lengths. A unique distribution of inherited ataxias in Peru requires specific screening panels, considering SCA10 as first line of local diagnosis guidelines.

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KW - Friedreich ataxia

KW - Inherited ataxias

KW - Penetrance

KW - Peru

KW - Spinocerebellar ataxia

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U2 - 10.1007/s12311-019-01098-2

DO - 10.1007/s12311-019-01098-2

M3 - Artículo

C2 - 31900855

AN - SCOPUS:85077629385

SN - 1473-4222

VL - 19

SP - 208

EP - 215

JO - Cerebellum

JF - Cerebellum

IS - 2

ER -

Genetic Analysis of Hereditary Ataxias in Peru Identifies SCA10 Families with Incomplete Penetrance

Abstract

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Keywords

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