Common Premutations in the General Population

Hammer, Monia; Singleton, Andrew B.

doi:10.1001/jamaneurol.2019.0216

Cited by 4 publications

(3 citation statements)

References 17 publications

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“…The suggestions that the IA of HTT plays a role in the development of bipolar disorder or is associated with a peculiar new non-motor phenotype in the spectrum of HD disorder are both fascinating hypotheses that need to be clarified through a larger study of bipolar patients and their relatives. Regardless, beyond the interpretation of the role played by the HTT gene in the development of bipolar symptoms, the identification of IA carriers among this Italian cohort of bipolar patients has important implications for both patients and their families: patients can be at risk of developing a complete HD phenotype [ 11 , 13 ], and family members should be made aware of their increased risk of developing behavioral disturbances [ 10 ] or inheriting a pathological expanded HTT gene [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

“…HD is transmitted in an autosomal dominant manner, but new mutations can be generated in the offspring via the elongation of unstable alleles falling in the range 27–35 repeats, which are defined as intermediate alleles (IA) [ 6 ]. The percentage of IA has been variably estimated to be between 0.45 and 8.7% [ 7 , 8 ] in the healthy population.…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have demonstrated that the length of CAG repeats can influence the risk of the development of depressive symptoms [ 24 ], and major depression could be a pre-motor phenotype of HD [ 25 ]. Subjects with expanded HTT alleles and pre-motor psychiatric symptoms could be misdiagnosed as having primary psychiatric disease, while their early identification would imply different clinical management, such as specific clinical follow-up, tailored treatment [ 26 ] and the genetic counseling of family members [ 6 , 11 , 13 ]. In the present study, we analyzed the HTT gene in a psychiatric cohort of patients affected by bipolar disorder in order to identify pre-motor HD patients and evaluate whether the length of CAG repeats may influence or contribute to the development of bipolar disorder.…”

Section: Introductionmentioning

confidence: 99%

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The Huntington’s Disease Gene in an Italian Cohort of Patients with Bipolar Disorder

Ferrari,

Capacci,

Bagnoli

et al. 2023

Genes

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Background and objectives: Huntington’s disease (HD) is characterized by motor, cognitive and psychiatric manifestations and caused by an expansion of CAG repeats over 35 triplets on the huntingtin (HTT) gene. However, expansions in the range 27–35 repeats (intermediate allele) can be associated with pathological phenotypes. The onset of HD is conventionally defined by the onset of motor symptoms, but psychiatric disturbances can precede the motor phase by up to twenty years. The aims of the present study are to identify HD patients in the pre-motor phase of the disease among patients diagnosed with bipolar disorders and evaluate any differences between bipolar patients carrying the normal HTT allele and patients with the expanded HTT gene. Methods: We assessed the HTT genotype in an Italian cohort of 69 patients who were affected by either type 1 or type 2 bipolar disorder. Results: No patient was found to be a carrier of the pathological HTT allele, but 10% of bipolar subjects carried an intermediate allele. Carriers of the intermediate allele were older at the onset of psychiatric symptoms than non-carriers. Conclusion: The pathological HTT gene was not associated with bipolar disorder, while we found a higher frequency of the intermediate allele among the bipolar population with respect to healthy controls. The identification of this subset of bipolar subjects has implications for the clinical management of patients and their family members and promotes further investigation into possible pathological mechanisms common to both HD and bipolar disorder.

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