Huntington disease (HD) is an autosomal dominant disease characterized by motor, behavioral, and cognitive symptoms, caused by the pathological expansion of more than 35 CAG/CAA repeats in the HTT gene. We describe the phenotype of a patient compatible with HD. Several family members were reported as affected, and a paternal cousin and his daughter carried 39 and 42 CAG/CAA. HD genetic testing in proband showed homozygosity for a 14 CAG/CAA allele. Considering the phenotype and family history, HTT gene sequence was performed, revealing heterozygosity for the c.51C>G variant that changes the last nucleotide before the CAG tract, causing misannealing of forward primer (HD344) and dropout of the expanded allele. Polymerase chain reaction (PCR) analysis performed with an alternative forward primer demonstrated a 41 CAG/CAA allele. The c.51C>G variant was not detected in the affected cousin, thus suggesting a de novo occurrence. The lack of biological samples from the proband father and grandmother prevented further investigations to establish in which family member the variant occurred. These data indicate that patients presenting HD phenotype, and homozygous for a normal HTT CAG/CAA allele should be thoroughly evaluated for the presence of a genetic variant, even de novo, within the repeat region that may hamper genetic diagnosis.

中文翻译：

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缺少亨廷顿病的病理学扩展：扩展的等位基因上的新的c.51C> G变异导致家族内等位基因缺失

亨廷顿病（HD）是一种常染色体显性遗传疾病，其特征在于运动，行为和认知症状，由HTT基因中超过35个CAG / CAA重复序列的病理扩展引起。我们描述了与高清兼容的患者的表型。据报道有几位家庭成员受到影响，一位堂兄及其女儿携带了39和42 CAG / CAA。先证者的高清基因测试显示14个CAG / CAA等位基因是纯合的。考虑到表型和家族史，HTT进行了基因序列分析，揭示了c.51C> G变异体的杂合性，该变异体改变了CAG通道之前的最后一个核苷酸，从而导致正向引物（HD344）的错误退火和扩展等位基因的缺失。用另一种正向引物进行的聚合酶链反应（PCR）分析显示41个CAG / CAA等位基因。在受影响的表亲中未检测到c.51C> G变体，因此表明从头发生。先证者父亲和祖母缺乏生物样品，这阻止了进一步的调查来确定变异发生在哪个家庭成员中。这些数据表明，患者表现出HD表型，并且对于正常的HTT是纯合的 应该彻底评估CAG / CAA等位基因在重复区域内是否存在遗传变异，甚至是从头存在，这可能会妨碍遗传诊断。