Genetic heterogeneity in patients with Bartter syndrome type 1.

Bartter syndrome (BS) type 1 is an autosomal recessive kidney disorder caused by loss­of­function mutations in the solute carrier family 12 member 1 (SLC12A1) gene. To date, 72 BS type 1 patients harboring SLC12A1 mutations have been documented. Of these 144 alleles studied, 68 different disease­causing mutations have been detected in 129 alleles, and no mutation was detected in the remaining 15 alleles. The mutation types included missense/nonsense mutations, splicing mutations and small insertions and deletions ranging from 1 to 4 nucleotides. A large deletion encompassing a whole exon in the SLC12A1 gene has not yet been reported. The current study initially identified an undocumented homozygous frameshift mutation (c.1833delT) by Sanger sequencing analysis of a single infant with BS type 1. However, in a subsequent analysis, the mutation was detected only in the father's DNA. Upon further investigation using a next­generation sequencing approach, a deletion in exons 14 and 15 in both the patient and patient's mother was detected. The deletion was subsequently confirmed by use of a long­range polymerase chain reaction and was determined to be 3.16 kb in size based on sequencing of the junction fragment. The results of the present study demonstrated that pathogenic variants of SLC12A1 are heterogeneous. Large deletions appear to serve an etiological role in BS type 1, and may be more prevalent than previously thought.

Muscle activity and co-contraction of musculoskeletal model during steering maneuver.

In this study a musculoskeletal model of driver steering maneuver was established. The model was driven by the steering angle and steering torque when performing typical steering test. The simulation was calculated using inverse dynamics. Maximum muscle activity and the muscle activity of each muscle were studied afterwards. The key muscles that generated steering torque were scapular portion of deltoid, infraspinatus, latissimus dorsi, subscapularis, triceps long head and triceps lateral head. Muscle co-contraction was analyzed quantitatively and was significantly different from muscle activity. This paper presents a preliminary research on the mechanical properties of upper limb muscles during steering maneuver. The results can serve as references for vehicle design and performance evaluation using the physiological characteristics of drivers.