Analysis of a very large trinucleotide repeat in a patient with juvenile Huntington’s disease

Nance, Martha; Mathias-Hagen, V.; Breningstall, Galen N.; Wick, Myra J.; McGlennen, Ronald C.

doi:10.1212/wnl.52.2.392

Cited by 106 publications

(99 citation statements)

References 9 publications

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“…10 The longest CAG repeat found by Seneca et al 18 was the repeat with 214 CAG copies. Nance et al 19 reported an individual with juvenile-onset HD who had 250 CAG repeats. This patient had a maternal history of HD, but the mother's allele could not be determined because a DNA sample was not available.…”

Section: Discussionmentioning

confidence: 99%

Haplotype analysis of the CAG and CCG repeats in 21 Brazilian families with Huntington’s disease

et al. 2012

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We studied the allelic profile of CAG and CCG repeats in 61 Brazilian individuals in 21 independent families affected by Huntington's disease (HD). Thirteen individuals had two normal alleles for HD, two had one mutable normal allele and no HD phenotype, and forty-six patients carried at least one expanded CAG repeat allele. Forty-five of these individuals had one expanded allele and one individual had one mutable normal allele (27 CAG repeats) and one expanded allele (48 CAG repeats). Eleven of these forty-five subjects had a mutant allele with reduced penetrance, and thirty-four patients had a mutant allele with complete penetrance. Inter-and intragenerational investigations of CAG repeats were also performed. We found a negative correlation between the number of CAG repeats and the age of disease onset (r ¼ À0.84; Po0.001) and no correlation between the number of CCG repeats and the age of disease onset (r ¼ 0.06). We found 40 different haplotypes and the analysis showed that (CCG) 10 was linked to a CAG normal allele in 19 haplotypes and to expanded alleles in two haplotypes. We found that (CCG) 7 was linked to expanded CAG repeats in 40 haplotypes (95.24%) and (CCG) 10 was linked to expanded CAG repeats in only two haplotypes (4.76%). Therefore, (CCG) 7 was the most common allele in HD chromosomes in this Brazilian sample. It was also observed that there was a significant association of (CCG) 7 with the expanded CAG alleles (v 2 ¼ 6.97, P ¼ 0.0084). Worldwide, the most common CCG alleles have 7 or 10 repeats. In Western Europe, (CCG) 7 is the most frequent allele, similarly to our findings.

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Section: Discussionmentioning

confidence: 99%

Haplotype analysis of the CAG and CCG repeats in 21 Brazilian families with Huntington’s disease

et al. 2012

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“…Although the upper limit of detection is not known, alleles carrying ~115 CAG repeats have been amplified by PCRbased methods, 26 whereas alleles carrying more than ~125 CAG repeats appear to be refractory to reproducible amplification. 15 Polymorphisms surrounding or within the CAG tract have been identified and have a collective frequency of >1% in patients referred for HD testing.…”

Section: Methodological Considerationsmentioning

confidence: 99%

“…14 The largest expanded HD allele detected to date carries ~250 CAG repeats in a patient with juvenile-onset disease. 15 Mosaicism. Mosaicism attributable to both mitotic and meiotic instability has been described in brain and sperm, and it appears to be more pronounced in juvenile-onset cases of HD associated with larger CAG expansions.…”

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confidence: 99%

American College of Medical Genetics and Genomics Standards and Guidelines for Clinical Genetics Laboratories, 2014 edition: technical standards and guidelines for Huntington disease

Bean

Bayrak-Toydemir

2014

Genetics in Medicine

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“…The largest reported intergenerational expansion is þ160 repeats wherein a father with 54 repeats had a child with 214 repeats [Seneca et al, 2004]. Nance et al [1999] reported a juvenile-onset HD case of 250 repeats in a patient with a maternal history of HD; however, a DNA sample was not available to confirm the mother's allele size. Laccone and Christian [2000] described two sisters with HD in which they inherited maternal expansions of þ21 and þ30 repeats.…”

Section: Introductionmentioning

confidence: 99%

Juvenile onset Huntington disease resulting from a very large maternal expansion

Nahhas

Garbern

Krajewski

et al. 2005

American J of Med Genetics Pt A

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We report a 5½‐year‐old girl with a maternal family history of Huntington disease (HD), who presented clinically with unbalanced gait, impaired speech, and increasing difficulty with fine motor control. Onset of symptoms began at the age of 3½ years. The suspected diagnosis of juvenile HD, based upon her family history, was confirmed by DNA analysis. At age 7, the patient died secondary to complications of her underlying disorder. Juvenile‐onset Huntington disease is uncommon, predominantly transmitted by fathers and is always associated with very large expansions of the CAG repeat. Interestingly, this patient inherited a large CAG size expansion from her mother, who herself had symptoms of HD at the age of 18. Molecular analysis revealed that the mother had 70 CAG repeats whereas our patient had ∼130 CAG repeats. This is the largest reported CAG expansion from a maternal transmission that has been confirmed molecularly and it demonstrates that very large expansions can also occur through the maternal lineage. © 2005 Wiley‐Liss, Inc.

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Analysis of a very large trinucleotide repeat in a patient with juvenile Huntington’s disease

Cited by 106 publications

References 9 publications

Haplotype analysis of the CAG and CCG repeats in 21 Brazilian families with Huntington’s disease

Haplotype analysis of the CAG and CCG repeats in 21 Brazilian families with Huntington’s disease

American College of Medical Genetics and Genomics Standards and Guidelines for Clinical Genetics Laboratories, 2014 edition: technical standards and guidelines for Huntington disease

Juvenile onset Huntington disease resulting from a very large maternal expansion

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