Clinical manifestations of intermediate allele carriers in Huntington disease

Objective: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry. Methods: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores. Results: Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p 0.002). Conclusions: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling. ClinicalTrials.gov identifier: NCT01590589

Clinical and genetic characteristics of late-onset Huntington's disease

Background: The frequency of late-onset Huntington's disease (&gt;59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30\u201350 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of 6435 or a UHDRS motor score of 645 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P &lt;.001). Overall motor and cognitive performance (P &lt;.001) were worse, however only disease motor progression was slower (coefficient, 120.58; SE 0.16; P &lt;.001) compared to the common-onset group. Repeat size was significantly lower in the late-onset (n = 40.8; SD 1.6) compared to common-onset (n = 44.4; SD 2.8) (P &lt;.001). Fewer late-onset patients (n = 451) had a positive family history compared to common-onset (n = 2940) (P &lt;.001). Conclusions: Late-onset patients present more frequently with gait and balance problems as first symptom, and disease progression is not milder compared to common-onset HD patients apart from motor progression. The family history is likely to be negative, which might make diagnosing HD more difficult in this population. However, the balance and gait problems might be helpful in diagnosing HD in elderly patients

Notes for genera – Ascomycota

Knowledge of the relationships and thus the classification of fungi, has developed rapidly with increasingly widespread use of molecular techniques, over the past 10--15 years, and continues to accelerate. Several genera have been found to be polyphyletic, and their generic concepts have subsequently been emended. New names have thus been introduced for species which are phylogenetically distinct from the type species of particular genera. The ending of the separate naming of morphs of the same species in 2011, has also caused changes in fungal generic names. In order to facilitate access to all important changes, it was desirable to compile these in a single document. The present article provides a list of generic names of Ascomycota (approximately 6500 accepted names published to the end of 2016), including those which are lichen-forming. Notes and summaries of the changes since the last edition of `Ainsworth Bisby's Dictionary of the Fungi' in 2008 are provided. The notes include the number of accepted species, classification, type species (with location of the type material), culture availability, life-styles, distribution, and selected publications that have appeared since 2008. This work is intended to provide the foundation for updating the ascomycete component of the ``Without prejudice list of generic names of Fungi'' published in 2013, which will be developed into a list of protected generic names. This will be subjected to the XIXth International Botanical Congress in Shenzhen in July 2017 agreeing to a modification in the rules relating to protected lists, and scrutiny by procedures determined by the Nomenclature Committee for Fungi (NCF). The previously invalidly published generic names Barriopsis, Collophora (as Collophorina), Cryomyces, Dematiopleospora, Heterospora (as Heterosporicola), Lithophila, Palmomyces (as Palmaria) and Saxomyces are validated, as are two previously invalid family names, Bartaliniaceae and Wiesneriomycetaceae. Four species of Lalaria, which were invalidly published are transferred to Taphrina and validated as new combinations. Catenomycopsis Tibell Constant. is reduced under Chaenothecopsis Vain., while Dichomera Cooke is reduced under Botryosphaeria Ces. De Not. (Art. 59)