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Copy neutral segments with allelic homozygosity, also known as regions of homozygosity (ROHs), are frequently identified in cases interrogated by oligonucleotide single-nucleotide polymorphism (oligo-SNP) microarrays. Presence of ROHs may be because of parental relatedness, chromosomal recombination or rearrangements and provides important clues regarding ancestral homozygosity, consanguinity or uniparental disomy. In this study of 14 574 consecutive cases, 832 (6%) were found to harbor one or more ROHs over 10 Mb, of which 651 cases (78%) had multiple ROHs, likely because of identity by descent (IBD), and 181 cases (22%) with ROHs involving a single chromosome. Parental relatedness was predicted to be first degree or closer in 5%, second in 9% and third in 19%. Of the 181 cases, 19 had ROHs for a whole chromosome revealing uniparental isodisomy (isoUPD). In all, 25 cases had significant ROHs involving a single chromosome; 5 cases were molecularly confirmed to have a mixed iso- and heteroUPD15 and 1 case each with segmental UPD9pat and segmental UPD22mat; 17 cases were suspected to have a mixed iso- and heteroUPD including 2 cases with small supernumerary marker and 2 cases with mosaic trisomy. For chromosome 15, 12 (92%) of 13 molecularly studied cases had either Prader-Willi or Angelman syndrome. Autosomal recessive disorders were confirmed in seven of nine cases from eight families because of the finding of suspected gene within a ROH. This study demonstrates that ROHs are much more frequent than previously recognized and often reflect parental relatedness, ascertain autosomal recessive diseases or unravel UPD in many cases.

Whole-genome oligonucleotide single-nucleotide polymorphism (oligo-SNP) arrays enable simultaneous interrogation of copy number variations (CNVs), copy neutral regions of homozygosity (ROH) and uniparental disomy (UPD). Structural variation in the human genome contributes significantly to genetic variation, and often has deleterious effects leading to disease causation. Co-occurrence of CNV and regions of allelic homozygosity in tandem involving the same chromosomal arm are extremely rare. Replication-based mechanisms such as microhomology-mediated break-induced replication (MMBIR) are recent models predicted to induce structural rearrangements and gene dosage aberrations; however, supportive evidence in humans for one-ended DNA break repair coupled with MMBIR giving rise to interstitial copy number gains and distal loss of heterozygosity has not been documented. We report on the identification and characterization of two cases with interstitial triplication followed by uniparental isodisomy (isoUPD) for remainder of the chromosomal arm. Case 1 has a triplication at 9q21.11-q21.33 and segmental paternal isoUPD for 9q21.33-qter, and presented with citrullinemia with a homozygous mutation in the argininosuccinate synthetase gene (ASS1 at 9q34.1). Case 2 has a triplication at 22q12.1-q12.2 and segmental maternal isoUPD 22q12.2-qter, and presented with hearing loss, mild dysmorphic features and bilateral iris coloboma. Interstitial triplication coupled with distal segmental isoUPD is a novel finding that provides human evidence for one-ended DNA break and replication-mediated repair. Both copy number gains and isoUPD may contribute to the phenotype. Significantly, these cases represent the first detailed genomic analysis that provides support for a MMBIR mechanism inducing copy number gains and segmental isoUPD in tandem.

Objective: To evaluate the therapeutic effect of combining ultrasound-guided hydrodilatation with hyaluronic acid and physical therapy compared with physical therapy alone in patients with adhesive capsulitis. Design: A prospective, single-blinded, randomised controlled trial. Setting: Single medical centre. Participants: Patients with adhesive capsulitis (N = 62) were divided into group A: ultrasound-guided hydrodilatation with hyaluronic acid + physical therapy (N = 31) and group B: physical therapy alone (N = 31). Interventions: Group A received three doses of ultrasound-guided hydrodilatation with hyaluronic acid-based injectates (20 mL in total). Both groups underwent structured physical therapy. Outcome measures: The primary outcome measure was Constant score, while secondary outcomes included Shoulder Pain and Disability Index score, numerical rating scale (at rest, night, and during motion), 36-item Short Form Health Survey, and range of motion of the shoulder. All measurements were collected at baseline, 6 weeks, and 12 weeks post-injection. Results: At week 12, the Constant scores were 68.29 ± 14.55 and 62.77 ± 14.44 for groups A and B, respectively. There was a greater reduction in the Constant score, Shoulder Pain and Disability Index, and numerical rating scale between the baseline and 6 weeks and between the baseline and 12 weeks in group A (Constant score: p < 0.05, Shoulder Pain and Disability Index: p < 0.01, and numerical rating scale: p < 0.05). Conclusion: The combination of ultrasound-guided hydrodilatation with hyaluronic acid in conjunction with physical therapy provides additional benefits compared to physical therapy alone for the treatment of adhesive capsulitis at up to 12 weeks. Trial registration: ClinicalTrials.gov: NCT02708706. [ABSTRACT FROM AUTHOR]

To investigate the efficacy of hydrodilatation with 40 mg triamcinolone acetonide (TA) compared with the same procedure with 10 mg TA in patients with adhesive capsulitis (AC) of the shoulders. Prospective, double-blind, randomized controlled trial with 12 weeks of follow-up. Tertiary care rehabilitation center. Eighty-four patients diagnosed with AC (N=84). Ultrasound guidance using (A) hydrodilatation with 4 mL of TA (40 mg)+4 mL 2% lidocaine hydrochloride+12 mL normal saline or (B) hydrodilatation with 1 mL of TA (10 mg)+4 mL 2% lidocaine hydrochloride+15 mL normal saline through the posterior glenohumeral recess. Shoulder Pain and Disability Index (SPADI), visual analog scale (VAS) for pain, and range of motion (ROM) at baseline and at 6 and 12 weeks after injection. Both groups experienced improvements in the SPADI score, VAS scores for pain, and ROM throughout the study period. However, group-by-time interactions were not significant for any outcome measurement at any follow-up time point. No adverse events were reported in either group. Ultrasound-guided hydrodilatation with 40 and 10 mg TA yielded similar improvements in SPADI, VAS score, and ROM at the 12-week follow-up. Considering the potential detrimental effects of corticosteroids on the adjacent cartilage and tendons, a low dose of TA would be preferable for ultrasound-guided hydrodilatation for AC. [ABSTRACT FROM AUTHOR]