TY - JOUR
T1 - Childhood-onset ataxia
T2 - Testing for large CAG-repeats in SCA2 and SCA7
AU - Mao, Rong
AU - Aylsworth, Arthur S.
AU - Potter, Nicholas
AU - Wilson, William G.
AU - Breningstall, Galen
AU - Wick, Myra J.
AU - Babovic-Vuksanovic, Dusica
AU - Nance, Martha
AU - Patterson, Marc C.
AU - Gomez, Christopher M.
AU - Snow, Karen
PY - 2002/7/15
Y1 - 2002/7/15
N2 - Infantile- and juvenile-onset spinal cerebellar ataxia (SCA) is associated with expansion of 130 to more than 200 CAG-repeats in the SCA2 and SCA7 genes. Routine clinical assays for SCA2 and SCA7, which use polymerase chain reaction (PCR) and denaturing PAGE (polyacrylamide gel electrophoresis), will not reliably detect such large expansions. An assay based on separation of PCR products on an agarose gel, blotting, and hybridization with a (CAG)6 oligonucleotide probe was used to test DNA from individuals more than 10 years of age who had a possible diagnosis of SCA. Among 25 cases, the PCR-blot assay confirmed the presence of SCA2 expansions between 230 and 500 repeats in four unrelated individuals, but did not detect any cases of extreme expansion in the SCA7 gene. The PCR-blot assay provides reliable detection of extreme expansion mutations. Routine incorporation of this assay in clinical laboratories may reveal that infantile-juvenile forms of SCA2 and SCA7 are more prevalent than previously recognized.
AB - Infantile- and juvenile-onset spinal cerebellar ataxia (SCA) is associated with expansion of 130 to more than 200 CAG-repeats in the SCA2 and SCA7 genes. Routine clinical assays for SCA2 and SCA7, which use polymerase chain reaction (PCR) and denaturing PAGE (polyacrylamide gel electrophoresis), will not reliably detect such large expansions. An assay based on separation of PCR products on an agarose gel, blotting, and hybridization with a (CAG)6 oligonucleotide probe was used to test DNA from individuals more than 10 years of age who had a possible diagnosis of SCA. Among 25 cases, the PCR-blot assay confirmed the presence of SCA2 expansions between 230 and 500 repeats in four unrelated individuals, but did not detect any cases of extreme expansion in the SCA7 gene. The PCR-blot assay provides reliable detection of extreme expansion mutations. Routine incorporation of this assay in clinical laboratories may reveal that infantile-juvenile forms of SCA2 and SCA7 are more prevalent than previously recognized.
KW - CAG-repeat
KW - SCA2
KW - SCA7
KW - Spinocerebellar ataxia
KW - Triplet repeat expansion
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U2 - 10.1002/ajmg.10467
DO - 10.1002/ajmg.10467
M3 - Article
C2 - 12116207
AN - SCOPUS:18444411305
SN - 0148-7299
VL - 110
SP - 338
EP - 345
JO - American journal of medical genetics
JF - American journal of medical genetics
IS - 4
ER -