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.

Cutaneous nerve entrapment plays an important role in neuropathic pain syndrome. Due to the advancement of ultrasound technology, the cutaneous nerves can be visualized by high-resolution ultrasound. As the cutaneous nerves course superficially in the subcutaneous layer, they are vulnerable to entrapment or collateral damage in traumatic insults. Scanning of the cutaneous nerves is challenging due to fewer anatomic landmarks for referencing. Therefore, the aim of the present article is to summarize the anatomy of the limb cutaneous nerves, to elaborate the scanning techniques, and also to discuss the clinical implications of pertinent entrapment syndromes of the medial brachial cutaneous nerve, intercostobrachial cutaneous nerve, medial antebrachial cutaneous nerve, lateral antebrachial cutaneous nerve, posterior antebrachial cutaneous nerve, superficial branch of the radial nerve, dorsal cutaneous branch of the ulnar nerve, palmar cutaneous branch of the median nerve, anterior femoral cutaneous nerve, posterior femoral cutaneous nerve, lateral femoral cutaneous nerve, sural nerve, and saphenous nerve.

The evaluation of circulating cell-free DNA by massively parallel shotgun or targeted sequencing to determine the risk of fetal aneuploidy has been rapid and extensive. Recent published studies have demonstrated the incremental value of the use of cell-free DNA for noninvasive prenatal testing (NIPT). 1 Various methods and technologies have been used for NIPT, with impressive results. In one study, NIPT demonstrated 100% sensitivity for both trisomy 21 and trisomy 18, with a specificity of ≥99.7% for both. 1 Data recently presented by two independent groups in 2013 2 and 2014 3 prompted us to review the concordance of results among cases with positive or negative NIPT results referred to Quest Diagnostics for confirmation with cytogenetic studies. MATERIALS AND METHODSWe evaluated the results from 109 consecutive specimens prenatally and/or postnatally studied by standard karyotyping, fluorescence in situ hybridization analysis (AneuVysion; Abbott Molecular/Vysis, Abbott Park, IL), and/or oligo-single-nucleotide polymorphism microarrays (CytoScanHD; Affymetrix, Santa Clara, CA) after NIPT. The NIPT providers were listed in 42 cases and included Panorama (Natera, San Carlos, CA; 20 cases), Harmony (Ariosa Diagnostics, San Jose, CA; 13 cases), MaterniT21 (Sequenom, San Diego, CA; 8 cases), and Verifi (Illumina, Redwood City, CA; 1 case). The most common initial NIPT-positive result was trisomy 21 (41 cases), followed by trisomy 18 (25 cases), trisomy 13 (16 cases), sex chromosome aneuploidy (16 cases), trisomy 16 (3 cases), monosomy 21 (2 cases), and 1 case each of triploidy and microdeletion of 22q11.2. Four samples negative for NIPT but positive for ultrasound findings were included. RESULTSCytogenetic results were positive for trisomy 21 in 38 of the 41 NIPT-positive cases (true-positive rate: 93%) and for trisomy 18 in 16 of the 25 NIPT-positive cases (true-positive rate: 64%) ( Table 1). The true-positive rate was only 44% (7/16 cases) for trisomy 13 and 38% (6/16 cases) for sex chromosome aneuploidy. A total of six cases with positive NIPT results for either monosomy 21, trisomy 16, triploidy, or 22q11.2 microdeletion had normal cytogenetic findings. Only one case had very-lowlevel mosaicism (~5-10%) for trisomy 16. Confined placental mosaicism was confirmed in two cases (2/105, 2%): one with 3% mosaic for trisomy 18 and another with a mosaic segmental uniparental disomy for 11p15.5-p11.2. A false-negative result for NIPT was identified in nonmosaic trisomies 9 and 21, a marker chromosome, and a mosaic sex chromosome aneuploidy.The findings from our laboratory and those presented by the above-mentioned two groups (n = 80 and n = 46) show that Purpose: Recent published studies have demonstrated the incremental value of the use of cell-free DNA for noninvasive prenatal testing with 100% sensitivity for trisomies 21 and 18 and a specificity of ≥99.7% for both. Data presented by two independent groups suggesting positive results by noninvasive prenatal testing were not confirmed by cytogenetic studies. Methods:C...

Purpose: Cluster-of-differentiation antigen 9 (CD9) protein, a member of the tetraspanin family, has been implicated in carcinogenesis of various human tumors. Although decreased expression of the CD82 tetraspanin protein, a close CD9 relative, is associated with prostate cancer progression, CD9 expression has not been analyzed in this malignancy. Experimental Design: CD9 expression in human prostatic adenocarcinoma was analyzed by immunohistochemistry on 167 primary tumors and 88 lymph node or bone metastases. CD9 cDNA was sequenced from two human prostate cancer cell lines, prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia (PIN), and normal prostatic tissues. Results: Although CD9 was detected in the epithelium of normal prostatic tissues, reduced or loss of CD9 expression within neoplastic cells was observed in 24% of 107 clinically localized primary adenocarcinomas, 85% of 60 clinically advanced primary adenocarcinomas, 85% of 65 lymph node metastases, and 65% of 23 bone metastases. Difference in CD9 expression between clinically localized and advanced diseases was highly significant (P < 1 Â 10 À7 ). Whereas there was no alteration of CD9 cDNA in normal tissues, all PC-3^derived cell lines, one PIN, and four prostatic adenocarcinomas harbored deletions in their CD9 cDNAs. Recurring CD9 point mutations were also found in PC-3M-LN4 cells, one PIN, and seven prostatic adenocarcinomas. Conclusions: CD9 expression is significantly reduced and even lost during prostate cancer progression. Moreover, deletions and mutations of the CD9 mRNA may be associated with loss of protein expression observed in tumor cells. Our data suggest that CD9 inactivation may play an important role in prostate cancer progression.

BackgroundCytogenetic evaluation of products of conception (POC) for chromosomal abnormalities is central to determining the cause of pregnancy loss. We compared the test success rates in various specimen types and the frequencies of chromosomal abnormalities detected by G-banding analysis with those found by Oligo-SNP chromosomal microarray analysis (CMA). We evaluated the benefit of CMA testing in cases of failed culture growth.MethodsConventional cytogenetic results of 5457 consecutive POC specimens were reviewed and categorized as placental villi, fetal parts, and unspecified POC tissue. The CMA was performed on 268 cases. Of those, 32 cases had concurrent G-banding results. The remaining 236 cases included 107 cases with culture failure and 129 cases evaluated by CMA alone.ResultsThe overall POC culture success rate was 75%, with the lowest for fetal parts (37.4%) and the highest for placental villi (81%). The abnormality rate was 58% for placental villi, but only 25% for fetal parts. Of the abnormalities detected, the most common were aneuploidies, including trisomy 16, triploidy, monosomy X, trisomy 22, trisomy 21 and trisomy 15, while the least encountered aneuploidies were trisomy 1, trisomy 19 and monosomies (except monosomy 21). Overall, POC specimens studied by CMA were successful in 89.6% of cases and yielded a 44.6% abnormality rate.ConclusionsPlacental villi yielded higher rates of culture success and a higher percentage of abnormal karyotypes than did other specimen types. The Oligo-SNP CMA method has demonstrated a viable alternative to the G-banding method in view of its advantages in detection of submicroscopic genomic aberrations, shorter turnaround time due to elimination of time required for culture and a higher test success rate.

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Exposure to space environment induces alterations in glucose and lipid metabolism that contribute to muscular atrophy, bone loss, and cardiovascular disorders. Intestinal microbiota is also changed, but its impact on spaceflight‐related metabolic disorder is not clear. We investigated the relationship between glucose metabolic changes and gut dysbiosis in a hind limb‐unloading (HU) mouse model, a well‐accepted ground‐based spaceflight analog. Impaired body weight gain, glucose intolerance, and peripheral insulin resistance were found in 2–4‐wk HU mice. Reduced abundance of gut Bifidobacterium spp. and Akkermansia muciniphila was observed within 3 d of HU. The ground‐based control (Ctrl) mice that were cohoused with HU mice showed similar patterns of dysbiosis and metabolic changes. Compared with the Ctrls, higher levels of plasma LPS‐binding protein and altered transcription of Tnfa and glucose metabolism‐related genes in the liver were observed in HU mice. The supplementation of Bifidobacterium spp. suppressed endotoxemia and liver inflammation and improved glucose tolerance in HU mice. The results indicate a close relationship between dysbiosis and altered glucose metabolism in the HU model and also emphasize the importance of evaluating intestinal microbiota in astronauts and its effect on glucose metabolism.—Wang, Y., Zhao, W., Shi, J., Wang, J., Hao, J., Pang, X., Huang, X., Chen, X., Li, Y., Jin, R., Ge, Q. Intestinal microbiota contributes to altered glucose metabolism in simulated microgravity mouse model. FASEB J. 33, 10140–10151 (2019). http://www.fasebj.org

Objective We evaluated the effects of platforms, size filter cutoffs, and targeted regions of cytogenomic microarray (CMA) on the detection of copy number variants (CNVs) and uniparental disomy (UPD) in prenatal diagnosis. Methods Five thousand twenty‐six consecutive prenatal specimens (>98% high‐risk pregnancy) were studied by high‐resolution CMA, with cutoffs of 50 kb for losses and 200 kb for gains in nontargeted regions and 20 kb for losses and 100 kb for gains in targeted regions. We assessed actual detection rates using the current assay as well as hypothetical detection rates using platforms with the same or lower resolution and smaller or larger cutoffs. Results The detection rate of our current assay was 11.2% (562 of 5026), including abnormal findings in 543 cases and likely pathogenic variants in 19. The hypothetical decrease in the overall detection of variants (excluding likely benign) and UPD ranged from 3.8% to 23.0%. For the subgroup of pathogenic and likely pathogenic CNVs < 1 Mb, the decrease of detection ranged from 2.7% to 24.3%. Conclusions These findings underscore the significant effects of chosen CMA platform, as well as size filter cutoffs and targeted regions used in data analysis, on detection of CNVs and UPDs in a cohort of prenatal cases.