The autosomal dominant progressive bifocal chorioretinal atrophy (PBCRA) disease locus has been mapped to chromosome 6q14-16.2 that overlaps the North Carolina macular dystrophy (NCMD) locus MCDR1. NCMD is a nonprogressive developmental macular dystrophy, in which variants upstream of PRDM13 have been implicated. Whole genome sequencing was performed to interrogate structural variants (SVs) and single nucleotide variants (SNVs) in eight individuals, six affected individuals from two families with PBCRA, and two individuals from an additional family with a related developmental macular dystrophy. A SNV (chr6:100,046,804T>C), located 7.8 kb upstream of the PRDM13 gene, was shared by all PBCRA-affected individuals in the disease locus. Haplotype analysis suggested that the variant arose independently in the two families. The two affected individuals from Family 3 were screened for rare variants in the PBCRA and NCMD loci. This revealed a de novo variant in the proband, 21 bp from the first SNV (chr6:100,046,783A>C). This study expands the Human Mutation. 2019;40:578-587. wileyonlinelibrary.com/journal/humu 578 |

Autosomal dominant North Carolina macular dystrophy (NCMD) is believed to represent a failure of macular development. The disorder has been linked to two loci, MCDR1 (chromosome 6q16) and MCDR3 (chromosome 5p15-p13). Recently, non-coding variants upstream of PRDM13 (MCDR1) and a duplication including IRX1 (MCDR3) have been identified. However, the underlying disease-causing mechanism remains uncertain. Through a combination of sequencing studies on eighteen NCMD families, we report two novel overlapping duplications at the MCDR3 locus, in a gene desert downstream of IRX1 and upstream of ADAMTS16. One duplication of 43 kb was identified in nine families (with evidence for a shared ancestral haplotype), and another one of 45 kb was found in a single family. Three families carry the previously reported V2 variant (MCDR1), while five remain unsolved. The MCDR3 locus is thus refined to a shared region of 39 kb that contains DNAse hypersensitive sites active at a restricted time window during retinal development. Publicly available data confirmed expression of IRX1 and ADAMTS16 in human fetal retina, with IRX1 preferentially expressed in fetal macula. These findings represent a major advance in our understanding of the molecular genetics of NCMD and provide insights into the genetic pathways involved in human macular development.

Background Poor gait and static balance performance may be associated with trunk muscles in individuals with Parkinson's disease. Aim The study aims at evaluating the effects of a home-based trunk exercise program on gait and balance performance in Parkinson's disease. Methods A randomized controlled trial was conducted with 28 individuals with Parkinson's disease with Hoehn & Yahr stage II–IV. The control group ( n = 14) performed upper and lower limb exercises, while the experimental group ( n = 14) engaged in a trunk exercise program. Both groups performed home-based exercises three times daily for 3 weeks. At the end of interventions (post-training) and 4 weeks after post-training (follow-up), static balance (force plate) and gait (motion capture system) were evaluated. Mixed analysis of variance compared time × group interaction ( α = 5%). Results No time × group interaction was observed in the center of pressure displacement, center of pressure mean velocity, and anteroposterior and mediolateral center of pressure range during bipedal support with eyes opened and closed; and gait speed, hip, knee, and ankle range of motion during gait analysis. No intragroup differences were found. Conclusion Trunk strengthening exercises did not improve gait and balance compared with upper and lower limb exercises. The non-adherence rate (33%) to the remote intervention may have also hindered our results.

The history of muscle biopsy dates back to 1860, when Duchenne first performed a biopsy on a patient with symptoms of myopathy (1) . Since then, the basic and clinical science of muscle and muscle disease has gone through three stages of development: the classical period, the modern stage and the molecular era.