A Recurrent Expansion of a Maternal Allele with 36 CAG Repeats Causes Huntington Disease in Two Sisters Franco Laccone, Wilhelm Christian The American.

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A Recurrent Expansion of a Maternal Allele with 36 CAG Repeats Causes Huntington Disease in Two Sisters Franco Laccone, Wilhelm Christian The American Journal of Human Genetics Volume 66, Issue 3, Pages 1145-1148 (March 2000) DOI: 10.1086/302810 Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 1 A, Pedigree of the family showing the genotype of the family. The two affected sisters harbor expanded alleles of 66 CAG repeats and 57 CAG repeats. The allele of the proband II1, with 15 CAG repeats and 10 CCG repeats, must be of paternal origin, since the mother (I1) does not carry any of them. Therefore, the allele with 66 CAG repeats is of maternal origin. The second proband (II2) carries an allele with 21 CAG repeats inherited from the father (I2) and, consequently, the expanded allele with 57 CAG repeats inherited from her mother. The analysis at locus D4S115 proves that the sisters inherited the same maternal chromosome 4 from the mother and that the genotyping at locus D4S2936 is compatible with the inheritance of the same maternal chromosome 4. The genotyping at locus D4S126 was not informative. B, Radiograph of the PCR analysis of the CAG repeats in the HD gene. Genomic blood DNA was amplified from two sisters and the parents, as described, and the products were separated on a 5% denaturing polyacrylamide gel. The father of II1 (lane 2) carries 20 and 21 CAG repeats. The mother (lane 3) has one allele with 18 CAG repeats and a second allele in the “mutable normal allele” range of 36 CAG repeats. In lane 1 is the large allele of ∼66 CAG repeats and the small one of 15 CAG repeats. In lane 4, the expanded allele is of ∼57 CAG repeats and the small of 21 CAG repeats. The marker is on the left (M13mp18). Asterisks (*) denote CAG alleles. The American Journal of Human Genetics 2000 66, 1145-1148DOI: (10.1086/302810) Copyright © 2000 The American Society of Human Genetics Terms and Conditions