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Huntington disease is a neurodegenerative disorder caused by a gene (HTT) with a unique feature of trinucleotide repeats ranging from 10 to 35 in healthy people; when expanded beyond 39 repeats, Huntington disease develops. Animal models demonstrate that HTT is vital to brain development; however, this has not been studied in humans. Moreover, evidence suggests that triplet repeat genes may have been vital in evolution of the human brain. Here we evaluate brain structure using magnetic resonance imaging and brain function using cognitive tests in a sample of school-aged children ages 6 to 18 years old. DNA samples were processed to quantify the number of CAG repeats within HTT. We find that the number of repeats in HTT, below disease threshold, confers advantageous changes in brain structure and general intelligence (IQ): the higher the number of repeats, the greater the change in brain structure, and the higher the IQ. The pattern of structural brain changes associated with HTT is strikingly different between males and females. HTT may confer an advantage or a disadvantage depending on the repeat length, playing a key role in either the evolution of a superior human brain or development of a uniquely human brain disease. © 2016 Wiley Periodicals, Inc.

Background: The Limb Girdle Muscular Dystrophies (LGMDs) are characterized by progressive weakness of the shoulder and hip girdle muscles as a result of over 30 different genetic mutations. This study is designed to develop clinical outcome assessments across the group of disorders. Methods/design: The primary goal of this study is to evaluate the utility of a set of outcome measures on a wide range of LGMD phenotypes and ability levels to determine if it would be possible to use similar outcomes between individuals with different phenotypes. We will perform a multi-center, 12-month study of 188 LGMD patients within the established Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Research Consortium, which is comprised of 11 sites in the United States and 2 sites in Europe. Enrolled patients will be clinically affected and have mutations in CAPN3 (LGMDR1), ANO5 (LGMDR12), DYSF (LGMDR2), DNAJB6 (LGMDD1), SGCA (LGMDR3), SGCB (LGMDR4), SGCD (LGMDR6), or SGCG (LGMDR5, or FKRP-related (LGMDR9). Discussion: To the best of our knowledge, this will be the largest consortium organized to prospectively validate clinical outcome assessments (COAs) in LGMD at its completion. These assessments will help clinical trial readiness by identifying reliable, valid, and responsive outcome measures as well as providing data driven clinical trial decision making for future clinical trials on therapeutic agents for LGMD. The results of this study will permit more efficient clinical trial design. All relevant data will be made available for investigators or companies involved in LGMD therapeutic development upon conclusion of this study as applicable. Trial registration: Clinicaltrials.gov NCT03981289; Date of registration: 6/10/2019. [ABSTRACT FROM AUTHOR]

Kalmia buxifolia (sand-myrtle, Ericaceae) is disjunctly distributed across the high-elevation rock outcrops of the southern Appalachians, upper monadnocks and pine savannas of the Carolina Piedmont and Coastal Plain, and the New Jersey Pine Barrens. Here, we sampled plants from each region and reconstructed the phylogeographic history of K. buxifolia to test a rock-outcrop Pleistocene refugium hypothesis, estimate the potential direction(s) and timing of migration, and date divergence from its alpine sister species, K. procumbens. We also assess whether isolation in these different environments has led to variation in intrinsic water-use efficiency. Dating analysis challenges the current hypothesis that rock-outcrop species are relics of Pleistocene refugia (< 18,000 ybp), placing the divergence of K. buxifolia and K. procumbens much earlier, in the late-Miocene (9.40 Ma). Chloroplast haplotype analysis indicates four potential refugial sites, with the most ancient on Mount LeConte in the Great Smoky Mountains, and point to an Appalachian corridor as the likely Pine Barrens colonization route. The sister species divergence time and population level divergences within K. buxifolia generally coincide with major climatic shifts from the late-Miocene to mid-Pleistocene. Results from carbon isotope discrimination indicate that plant water-use varies geographically within K. buxifolia, as does leaf morphology, although it is unclear whether this variation is due to genetic adaptation or phenotypic plasticity. These patterns of phylogenetic divergence and resulting ecophysiological diversity within K. buxifolia are significant for clarifying long-held questions about the biogeographic history and trait differentiation within this species. Further, our results suggest that high-elevation rock outcrop communities may have been inhabitated by northern-affinity species for much longer than previously assumed, and that subsequent population disjunction and isolation may have resulted in ecophysiological differentiation in these communities. [ABSTRACT FROM AUTHOR]

The gene (Huntingtin or HTT) causing Huntington’s disease (HD) is vital for development and is expressed throughout the brain and body lifelong. The mutant form (mHTT) may influence growth and development.To determine the impact of mHTT on human measures of growth, including height, weight and body mass index (BMI), between child and adolescent carriers of mHTT and control peers.Children ages 6–18 years of age (n = 186) at risk for HD were enrolled in the KidsHD study. For research purposes only, genetic testing was performed to classify participants as Gene-Expanded (GE = 78) or as Gene Non-Expanded (GNE = 108). Outcome measures included height, weight, and body mass index (BMI). Mixed models were used to determine if non-linear age trends differed between groups for BMI, height and weight.Differences were seen in the trajectory of BMI in which the GE group reached a plateau in late adolescence with no further increase, compared with a nearly linear increase in the GNE group. There was a significant sex interaction pattern where GE males were taller than GNE males in adolescence, in the presence of similar weight. In contrast, GE females weighed significantly less than their GNE counterparts in adolescence, in the presence of similar height.Measures of growth are abnormal in child and adolescent carriers of mHTT, decades before HD onset. Although further studies are needed for replication, the current findings suggest that developmental aberrations may be systemic and a vital part of disease pathology. [ABSTRACT FROM AUTHOR]

Background: The Limb Girdle Muscular Dystrophies (LGMDs) are characterized by progressive weakness of the shoulder and hip girdle muscles as a result of over 30 different genetic mutations. This study is designed to develop clinical outcome assessments across the group of disorders., Methods/design: The primary goal of this study is to evaluate the utility of a set of outcome measures on a wide range of LGMD phenotypes and ability levels to determine if it would be possible to use similar outcomes between individuals with different phenotypes. We will perform a multi-center, 12-month study of 188 LGMD patients within the established Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Research Consortium, which is comprised of 11 sites in the United States and 2 sites in Europe. Enrolled patients will be clinically affected and have mutations in CAPN3 (LGMDR1), ANO5 (LGMDR12), DYSF (LGMDR2), DNAJB6 (LGMDD1), SGCA (LGMDR3), SGCB (LGMDR4), SGCD (LGMDR6), or SGCG (LGMDR5, or FKRP-related (LGMDR9)., Discussion: To the best of our knowledge, this will be the largest consortium organized to prospectively validate clinical outcome assessments (COAs) in LGMD at its completion. These assessments will help clinical trial readiness by identifying reliable, valid, and responsive outcome measures as well as providing data driven clinical trial decision making for future clinical trials on therapeutic agents for LGMD. The results of this study will permit more efficient clinical trial design. All relevant data will be made available for investigators or companies involved in LGMD therapeutic development upon conclusion of this study as applicable., Trial Registration: clinicaltrials.gov NCT03981289; Date of registration: 6/10/2019., Competing Interests: Competing Interests- None of the authors have a competing financial or non-financial interest with this study.