Browsing by Subject "Karyotype"

Now showing 1 - 2 of 2
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    Characterization of Spontaneous and Induced Puberty in Girls with Turner Syndrome
    (American Association of Clinical Endocrinologists, 2017-07) Folsom, Lisal J.; Slaven, James E.; Nabhan, Zeina M.; Eugster, Erica A.; Medicine, School of Medicine
    OBJECTIVE: To characterize puberty in girls with Turner syndrome (TS) and determine whether specific patient characteristics are associated with the timing of menarche. We also sought to compare spontaneous versus induced puberty in these patients. METHODS: Medical records of girls followed in our Pediatric Endocrine clinic for TS from 2007 to 2015 were reviewed. RESULTS: Fifty-three girls were included, of whom 10 (19%) achieved menarche spontaneously and 43 (81%) received hormone replacement therapy (HRT). Of girls receiving HRT, a younger age at estrogen initiation correlated with a longer time to menarche (P = .02), and a mosaic karyotype was associated with a shorter time to menarche (P = .02), whereas no relationship was seen for body mass index, estrogen regimen, or maternal age at menarche. Nineteen girls (44%) receiving HRT had bleeding on estrogen alone at a wide dose range and were more likely to be on transdermal than oral preparations (P = .01). Girls with spontaneous puberty achieved menarche at a younger age (P<.01) and were more likely to have mosaic TS (P = .02). CONCLUSION: Significant variability in the timing of menarche exists among girls with TS. However, age at pubertal induction and karyotype were significantly correlated with age at menarche in our patients. A wide range of estrogen doses is seen in girls who bleed prior to progesterone, suggesting extreme variability in estrogen sensitivity among patients with TS. Girls achieving spontaneous menarche are younger and more likely to have a mosaic karyotype than those with induced menarche. Large-scale prospective studies are needed to confirm these results.
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    Systematic evaluation of genome sequencing for the diagnostic assessment of autism spectrum disorder and fetal structural anomalies
    (Elsevier, 2023) Lowther, Chelsea; Valkanas, Elise; Giordano, Jessica L.; Wang, Harold Z.; Currall, Benjamin B.; O'Keefe, Kathryn; Pierce-Hoffman, Emma; Kurtas, Nehir E.; Whelan, Christopher W.; Hao, Stephanie P.; Weisburd, Ben; Jalili, Vahid; Fu, Jack; Wong, Isaac; Collins, Ryan L.; Zhao, Xuefang; Austin-Tse, Christina A.; Evangelista, Emily; Lemire, Gabrielle; Aggarwal, Vimla S.; Lucente, Diane; Gauthier, Laura D.; Tolonen, Charlotte; Sahakian, Nareh; Stevens, Christine; An, Joon-Yong; Dong, Shan; Norton, Mary E.; MacKenzie, Tippi C.; Devlin, Bernie; Gilmore, Kelly; Powell, Bradford C.; Brandt, Alicia; Vetrini, Francesco; DiVito, Michelle; Sanders, Stephan J.; MacArthur, Daniel G.; Hodge, Jennelle C.; O'Donnell-Luria, Anne; Rehm, Heidi L.; Vora, Neeta L.; Levy, Brynn; Brand, Harrison; Wapner, Ronald J.; Talkowski, Michael E.; Medical and Molecular Genetics, School of Medicine
    Short-read genome sequencing (GS) holds the promise of becoming the primary diagnostic approach for the assessment of autism spectrum disorder (ASD) and fetal structural anomalies (FSAs). However, few studies have comprehensively evaluated its performance against current standard-of-care diagnostic tests: karyotype, chromosomal microarray (CMA), and exome sequencing (ES). To assess the clinical utility of GS, we compared its diagnostic yield against these three tests in 1,612 quartet families including an individual with ASD and in 295 prenatal families. Our GS analytic framework identified a diagnostic variant in 7.8% of ASD probands, almost 2-fold more than CMA (4.3%) and 3-fold more than ES (2.7%). However, when we systematically captured copy-number variants (CNVs) from the exome data, the diagnostic yield of ES (7.4%) was brought much closer to, but did not surpass, GS. Similarly, we estimated that GS could achieve an overall diagnostic yield of 46.1% in unselected FSAs, representing a 17.2% increased yield over karyotype, 14.1% over CMA, and 4.1% over ES with CNV calling or 36.1% increase without CNV discovery. Overall, GS provided an added diagnostic yield of 0.4% and 0.8% beyond the combination of all three standard-of-care tests in ASD and FSAs, respectively. This corresponded to nine GS unique diagnostic variants, including sequence variants in exons not captured by ES, structural variants (SVs) inaccessible to existing standard-of-care tests, and SVs where the resolution of GS changed variant classification. Overall, this large-scale evaluation demonstrated that GS significantly outperforms each individual standard-of-care test while also outperforming the combination of all three tests, thus warranting consideration as the first-tier diagnostic approach for the assessment of ASD and FSAs.