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2121 citation(s) found for "Ma, Julie".

The Effects of Speech Compression Algorithms on the Intelligibility of Two Individuals With Dysarthric Speech
Sandoval, Steven , Berisha, Visar , Lansford, Kaitlin L. , Utianski, Rene L. , Liss, Julie , Berisha, Visar

American Journal of Speech-Language Pathology | December 5, 2018 | Volume: 28 | Issue: 1 | Pages: 195-203

10.1044/2018_ajslp-18-0081 | PMID 30515518 Get It

Purpose Telemedicine, used to offset disparities in access to speech-language therapy, relies on technology that utilizes compression algorithms to transmit signals efficiently. These algorithms have been thoroughly evaluated on healthy speech; however, the effects of compression algorithms on the intelligibility of disordered speech have not been adequately explored. Method This case study assessed acoustic and perceptual effects of resampling and speech compression (i.e., transcoding) on the speech of 2 individuals with dysarthria. Forced-choice vowel identification and transcription tasks were utilized, completed by 20 naive undergraduate listeners. Results Results showed relative improvements and decrements in intelligibility, on various measures, based on the speakers' acoustic profiles. The transcoding of the speech compression algorithm resulted in an enlarged vowel space area and associated improvements in vowel identification for 1 speaker and a smaller vowel space area and decreased vowel identification for the other speaker. Interestingly, there was an overall decrease in intelligibility in the transcription task in this condition for both speakers. Conclusions There is a complex interplay between dysarthria and compression algorithms that warrants further exploration. The findings suggest that it is critical to be mindful of apparent changes in intelligibility secondary to compression algorithms necessary for practicing telemedicine. Supplemental Material https://doi.org/10.23641/asha.7291940
Assessment of Test Performance and Potential for Environmental Contamination Associated with a Point-of-Care Molecular Assay for Group A Streptococcus in an End User Setting
Myhre, Nikki K., Murray, Martha A. , McDonah, Margaret R. , Myers, Jane F., Maxson, Julie, Meek, Alicia M., Espy, Mark J., Furst, Joseph W. , Karon, Brad S. , Binnicker, Matthew J. , Donato, Leslie J. , Maxson, Julie A, Myhre, Nikki K.

Journal of Clinical Microbiology | December 4, 2018 | Volume: 57 | Issue: 2 | Pages: No page available

10.1128/jcm.01629-18 | PMID 30518542 Get It

Although U.S. Food and Drug Administration-approved and CLIA-waived point-of-care (POC) molecular systems are being implemented in routine clinical practice, instrument reliability, test performance in the hands of end users, and the potential for environmental contamination resulting from use of POC molecular systems have not been extensively evaluated.
Fractional CO2 laser therapy for genitourinary syndrome of menopause (GSM) in survivors of breast cancer (BC).
Zvinovski, Filadelfiya , Hudson, Catherine O., Hundley, Andrew F., Evans, Cynthia, Suresh, Anupama , Stephens, Julie , Carpenter, Kristen M. , Ramaswamy, Bhuvaneswari , Reinbolt, Raquel E. , Williams, Nicole , Sardesai, Sagar , Loprinzi, Charles L. , Sardesai, Sagar , Quick, Allison , Noonan, Anne M. , VanDeusen, Jeffrey , Wesolowski, Robert , Stover, Daniel G. , Smith, Karen L. , Faubion, Stephanie S. , Lustberg, Maryam B.

Journal of Clinical Oncology | November 28, 2018 | Volume: 36 | Issue: 34_suppl | Pages: 202-202

10.1200/jco.2018.36.34_suppl.202 Get It

202 Background: Fractional CO2 laser therapy is an emerging treatment for GSM. The objective of this study was to determine the feasibility, tolerability and preliminary efficacy of fractional CO2 laser therapy in BC survivors. Methods: This was a single arm feasibility study of BC survivors with dyspareunia and/or vaginal dryness. Participants received three treatments with office-based fractional CO2 laser on at least 30 day intervals and returned for a one-month follow-up. Feasibility was defined as treatment completion without serious adverse events (SAE) in a minimum of 80% of patients. Primary efficacy was evaluated using the mean change (∆) in the score on the Vaginal Assessment Scale (VAS). Secondary efficacy endpoints included mean ∆ in scores on the Female Sexual Function Index (FSFI) and Urogenital Distress Inventory (UDI). Descriptive statistics (means and 95% confidence intervals (CI) for continuous variables and proportions for categorical variables) were used. Results: The study is ongoing with 65 patients enrolled. To date, 37 patients have completed all study treatments and follow-up. Median age for those who have completed treatment was 57 years (range 34-72). Most were ER/PR positive (78%) and Her 2 negative (81%) with stage I (43%) or II (41%) BC. Ninety-five percent were receiving endocrine therapy, most commonly aromatase inhibitors (73%). No SAEs were reported in the 37 patients who have completed study treatments and their outcomes are as follows. Based on the VAS, 78% reported moderate-severe dyspareunia and 89% reported moderate-severe vaginal dryness at baseline. At follow up, 28% reported moderate-severe dyspareunia and 28% reported moderate-severe vaginal dryness. The VAS score improved from baseline to follow up (mean ∆ 4.1; 95% CI [3.1, 5.1]). Similarly, the FSFI score improved (mean ∆ -10.0; 95% CI [-13.2, -6.9]) and the UDI score improved (mean ∆ -5.7; 95% CI [-10.1, -1.3]). Final efficacy analysis will be reported once all patients have completed all time points. Conclusions: Fractional CO2 laser treatment is feasible and tolerable in BC survivors and may reduce symptom burden from GSM. A randomized controlled trial with sham laser is currently in development. Clinical trial information: NCT03307044.
European Perspective on 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: Proceedings of an Interactive International Symposium
Luster, Markus , Aktolun, Cumali , Amendoeira, Isabel, Bible, Keith C. , Duntas, Leonidas H. , Handkiewicz-Junak, Daria , Hoffmann, Martha, Jarząb, Barbara , Musholt, Thomas J. , Newbold, Kate, Nixon, Iain J. , Sobrinho‐Simões, Manuel , Tuttle, R. Michael , Verburg, Frederik A. , Wartofsky, Leonard , Führer, Dagmar, Barczyński, Marcin , Elisei, Rossella , Leenhardt, Laurence , Smit, Johannes W. A. , Sosa, Julie Ann

Thyroid | November 28, 2018 | Volume: 29 | Issue: 1 | Pages: 7-26

10.1089/thy.2017.0129 | PMID 30484394 Get It

Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines
Théry, Clotilde , Witwer, Kenneth W. , Aïkawa, Elena , Alcaraz, María José , Anderson, Johnathon D. , Andriantsitohaina, Ramaroson , Antoniou, Anna , Arab, Tanina , Archer, Fabienne , Atkin‐Smith, Georgia K. , Ayre, D. Craig , Bach, Jean‐Marie , Bachurski, Daniel , Baharvand, Hossein , Balaj, Leonora , Baldacchino, Shawn , Bauer, Natalie , Baxter, Amy A. , Bebawy, Mary , Beckham, Carla, Zavec, Apolonija Bedina, Benmoussa, Abderrahim , Berardi, Anna C. , Bergese, Paolo , Bielska, Ewa , Blenkiron, Cherie , Bobis‐Wozowicz, Sylwia , Boilard, Éric , Boireau, Wilfrid , Bongiovanni, Antonella , Borràs, Francesc E. , Bösch, Steffi , Boulanger, Chantal M. , Breakefield, Xandra O. , Breglio, Andrew , Brennan, Meadhbh Á. , Brigstock, David R. , Brisson, Alain , Broekman, Marike L. D. , Bromberg, Jacqueline , Bryl‐Górecka, Paulina , Burger, Dylan , Busatto, Sara , Buschmann, Dominik , Buzás, Edit I. , Byrd, James Brian , Carter, David R. F. , Caruso, Sarah , Chamley, Lawrence W. , Cheng, Lesley , Chin, Andrew R., Clayton, Aled , Clerici, Stefano Piatto , Cocks, Alex, Cocucci, Emanuele , Coffey, Robert J., Cordeiro‐da‐Silva, Anabela , Couch, Yvonne , Coumans, Frank A. W., Coyle, Beth , Crescitelli, Rossella , Criado, Miriã Ferreira, D’Souza‐Schorey, Crislyn , Chaudhuri, Amrita Datta , Candia, Paola de , Santana, Eliezer F De , Wever, Olivier De , Portillo, Hernando A. del , Demaret, Tanguy , Deville, Sarah , Devitt, Andrew , Dhondt, Bert , Vizio, Dolores Di , Rubio, Ana Paula Domínguez , Dourado, Maurício Rocha , Driedonks, Tom A. P. , Duarte, Filipe V. , Duncan, Heather M. , Eichenberger, Ramon M. , Ekström, Karin M. , Andaloussi, Samir EL , Élie-Caille, Céline , Erdbrügger, Uta , Fatima, Farah , Fish, Jason E. , Flores‐Bellver, Miguel , Försönits, András, Frelet‐Barrand, Annie , Fricke, Fabia , Fuhrmann, Gregor , Gámez‐Valero, Ana , Gardiner, Chris , Gärtner, Kathrin , Gaudin, Raphaël , Gho, Yong Song , Giebel, Bernd , Gilbert, Caroline , Gimona, Mario , Giusti, Ilaria , Goberdhan, Deborah C. I. , Görgens, André , Gorski, Sharon M. , Greening, David W. , Gross, Julia Christina , Gualerzi, Alice , Gupta, Gopal N. , Gustafson, Dakota , Handberg, Aase , Haraszti, Reka A. , Harrison, Paul , Hegyesi, Hargita , Hendrix, An , Hill, Andrew F. , Hochberg, Fred H. , Hoffmann, Karl F. , Holder, Beth , Holthöfer, Harry , Hosseinkhani, Baharak , Hu, Guoku , Huang, Yiyao , Huber, Veronica , Hunt, Stuart , Ibrahim, Ahmed , Ikezu, Tsuneya , Inal, Jameel M. , Işın, Mustafa , Ivanova, Alena , Jackson, Hannah K. , Jacobsen, Søren , Jay, Steven M. , Jayachandran, Muthuvel , Jenster, Guido , Jiang, Lanzhou , Johnson, Suzanne M. , Jones, Jennifer , Jong, Ambrose, Jovanović‐Talisman, Tijana , Jung, Stephanie , Kalluri, Raghu , Kano, Shin‐ichi , Kaur, Sukhbir , Kawamura, Yumi , Keller, Evan T. , Khamari, Delaram , Khomyakova, Elena , Kierulf, Peter, Kim, Kwang Pyo , Kislinger, Thomas , Klingeborn, Mikael , Klinke, David J. , Kornek, Miroslaw , Kosanović, Maja , Kovács, Árpád Ferenc , Krämer‐Albers, Eva‐Maria , Krause, Mirja, Kurochkin, Igor V. , Kuypers, Sören , Laitinen, Saara , Langevin, Scott M. , Languino, Lucia R. , Lässer, Cecilia , Laurent, Louise C. , Lázaro‐Ibáñez, Elisa , Lay, Soazig Le , Lee, Myung‐Shin , Lee, Yi , Lemos, Débora S., Lenassi, Metka , Leszczynska, Aleksandra , Li, Isaac T. S. , Liao, Ke , Libregts, Sten F.W.M. , Ligeti, Erzsébet , Lim, Rebecca , Lim, Sai Kiang , Linē, Aija , Linnemannstöns, Karen, Llorente, Alicia , Lorenowicz, Magdalena J. , Lőrincz, Ákos M. , Lovett, Jason , Lowry, Michelle C., Loyer, Xavier , Lu, Quan , Łukomska, Barbara , Lunavat, Taral R. , Marcilla, Antonio , Mariani, Jacopo , Mariscal, Javier , Martens‐Uzunova, Elena S. , Martín‐Jaular, Lorena , Martínez, Maria Carmen , Martins, Vilma R. , Mathieu, Mathilde , Mathivanan, Suresh , Maugeri, Marco , McGinnis, Lynda K. , McVey, Mark J. , Meckes, David G. , Meehan, Katie , Jørgensen, Maléne Møller , Morhayim, Jess , Muraca, Maurizio , Musante, Luca , Mussack, Veronika , Muth, Dillon C. , Myburgh, Kathryn H. , Najrana, Tanbir , Nawaz, Muhammad , Nazarenko, Irina , Nejsum, Peter , Néri, Christian , Nolan, John P. , Hoen, Esther Nm Nolte-'t, Hooten, Nicole Noren , O’Grady, Tina , Ochiya, Takahiro , Olivier, Martin , Ortíz, Alberto , Ortiz, Luis A. , Osteikoetxea, Xabier , Østergaard, Ole , Ostrowski, Matías , Pegtel, D. Michiel , Peinado, Héctor , Perut, Francesca , Pfaffl, Michael W. , Phinney, Donald G. , Pieters, Bartijn C. H. , Pink, Ryan , Pisetsky, David S. , Strandmann, Elke Pogge von , Polakovičová, Iva , Poon, Ivan K. H. , Powell, Bonita H. , Prada, Ilaria , Pulliam, Lynn , Quesenberry, Peter J. , Radeghieri, Annalisa , Raffaı̈, Robert L. , Rak, Janusz , Ramirez, Marcel I. , Raposo, Graça , Rayyan, Morsi , Ricklefs, Franz , Roberts, David D. , Rodrigues, Sílvia C. , Rohde, Eva , Rome, Sophie , Rouschop, Kasper M.A. , Rughetti, Aurelia , Russell, Ashley E. , Sahoo, Susmita , Salas‐Huenuleo, Edison , Sánchez, Catherine , Saugstad, Julie A. , Saul, Meike J. , Schneider, Raphaël , Schøyen, Tine Hiorth , Scott, Aaron , Shahaj, Eriomina , Sharma, Shivani , Shatnyeva, Olga , Shekari, Faezeh , Shelke, Ganesh Vilas , Shiba, Kiyotaka , Siljander, Pia , Silva, Andreia , Skowronek, Agata, Snyder, Orman L., Sódar, Barbara W., Soekmadji, Carolina , Stahl, Philip D., Stoorvogel, Willem , Stott, Shannon L. , Strasser, Erwin , Tahara, Hidetoshi , Tewari, Muneesh , Timms, Kate , Tiwari, Swasti , Tixeira, Rochelle , Toh, Wei Seong , Tomasini, Richard , Tosar, Juan Pablo , Toxavidis, Vasilis, Urbanelli, Lorena , Vader, Pieter , Balkom, Bas WM van, Grein, Susanne G van der, Deun, Jan Van , Herwijnen, Martijn J. C. van , Keuren‐Jensen, Kendall Van , Niel, Guillaume van , Royen, Martin E. van , Wijnen, André J. van , Vasconcelos, M. Helena , Vechetti, Ivan J. , Vella, Laura J. , Velot, Émilie , Verweij, Frederik J. , Vestad, Beate , Viñas, Jose L. , Visnovitz, Tamás , Vukman, Krisztina V , Wahlgren, Jessica, Watson, Dionysios C. , Wauben, Marca H. M. , Weaver, Alissa M. , Webber, Jason , Weber, Viktoria , Wehman, Ann M. , Welsh, Joshua A , Wheelock, Åsa M. , Wiener, Zoltán , Witte, Leonie , Wolfram, Joy , Xagorari, Angeliki , Xander, Patrícia , Xu, Jing , Yan, Xiaomei , Yin, Hang , Yuana, Yuana, Zappulli, Valentina , Zárubová, Jana , Žėkas, Vytautas , Zhang, Jianye , Zhao, Zezhou , Zickler, Antje M. , Zimmermann, Pascale , Zivkovic, Angela M. , Zocco, Davide, Zuba‐Surma, Ewa , Malhi, Harmeet , Peinado, Héctor , van Wijnen, Andre J , Bergese, Paolo , Kim, Kwang Pyo , Ikezu, Tsuneya , Wolfram, Joy , Lenassi, Metka , Gualerzi, Alice , Nazarenko, Irina , Pink, Ryan , Siljander, Pia R-M , Welsh, Joshua A , Witwer, Kenneth W , Hill, Andrew F , Coyle, Beth , Saugstad, Julie A , Buch, Shilpa J. , Buck, Amy H. , Bussolati, Benedetta , Camussi, Giovanni , Chang, Yu‐Ting , Chen, Chihchen , Chen, Daiwen , Criado, Miriã Ferreira , Das, Saumya , Dieterich, Lothar C. , Dolo, Vincenza , Dominici, Massimo , Falcón‐Pérez, Juan Manuel , Gabrielsson, Susanne , Khvorova, Anastasia , Krasemann, Susanne , Kusuma, Gina Diamanta , Lannigan, Joanne , Laurent, Louise C , Lavieu, Grégory , Lombard, Catherine Anne , Lötvall, Jan , Maas, Sybren L. N. , Mertens, Inge , Minciacchi, Valentina R. , Möller, Andreas , Morales‐Kastresana, Aizea , Mullier, François , Neri, Tommaso , Nieuwland, Rienk , Nimrichter, Leonardo , O’Driscoll, Lorraine , O’Loghlen, Ana , Park, Jaesung , Raimondo, Stefania , Regev‐Rudzki, Neta , Robbins, Paul D. , Saá, Paula , Schiffelers, Raymond Michel , Shetty, Ashok Kumar , Soares, Rodrigo Pedro , Sotillo, Javier , Swift, Simon , Tkach, Mercedes , Torrecilhas, Ana Cláudia , Balkom, Bas W. M. van , Grein, Susanne G. van der, Veit, Tiago Degani , Weiss, Daniel J. , Wendt, Sebastian, Yáñez‐Mó, María , Zheng, Lei , Zheutlin, Alexander R. , Borràs, Francesc E , Martens-Uzunova, Elena S , Buzas, Edit I , Giebel, Bernd , Jones, Jennifer C , Ortiz, Alberto , Greening, David W

Journal of Extracellular Vesicles | November 24, 2018 | Volume: 7 | Issue: 1 | Pages: No page available

10.1080/20013078.2018.1535750 | PMID 30637094 Get It

ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell‐released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV‐associated functional activities. Finally, a checklist is provided with summaries of key points.
Hypothyroidism is associated with worse outcomes of hepatocellular carcinoma patients after liver transplantation
Zhang, Ning , Jin, Weidong , Zhou, Shuang-Nan , Yang, Ju Dong , Harmsen, William S. , Giama, Nasra H., Wongjarupong, Nicha , Watt, Kymberly D. , Therneau, Terry M. , Roberts, Lewis R. , Malhi, Harmeet , Roberts, Lewis R , Yang, Ju Dong , Heimbach, Julie K.

Cancer Medicine | November 19, 2018 | Volume: 7 | Issue: 12 | Pages: 5870-5878

10.1002/cam4.1797 | PMID 30453389 Get It

AbstractBackground/AimsHypothyroidism has been associated with hepatocellular carcinoma (HCC) incidence; however, the relationship between hypothyroidism and HCC patient outcomes is unclear. We investigated the impact of hypothyroidism on outcomes after liver transplantation for HCC.Materials and MethodsWe retrospectively studied HCC patients transplanted between January 2000 and December 2015. Hypothyroidism was defined as a thyroid‐stimulating hormone (TSH) level continuously greater than 5 mIU/L, a documented history of hypothyroidism, or treatment with thyroid hormone replacement therapy. Multivariate Cox regression was used to assess the impact of hypothyroidism on overall survival (OS) and recurrence‐free survival (RFS) adjusting for potential confounders. Subgroup analyses and interaction tests were conducted to compare the impact of hypothyroidism in different subgroups and assess for possible synergistic effects. Sensitivity analyses were performed among different cohorts to verify the stability of the results.ResultsA total of 343 HCC patients who underwent liver transplantation were included in the analysis. The primary analysis was conducted among 288 patients diagnosed with HCC prior to transplantation. Hypothyroidism was independently associated with worse OS and RFS, as was elevated TSH. The adjusted hazard ratio (AHR) of hypothyroidism was 2.45 (95% confidence interval [CI], 1.44‐4.18) for OS and 5.54 (2.36, 13.01) for RFS. The AHR of TSH for OS was 1.05 (1.02, 1.09) and 1.08 (1.03, 1.13) for RFS. No interaction was found among different subgroups categorized by etiology and comorbidity. The results were stable to sensitivity analyses.ConclusionHypothyroidism is associated with poorer overall and recurrence‐free survival of HCC patients receiving liver transplantation. These results require validation.
Models of Peer Support to Remediate Post-Intensive Care Syndrome: A Report Developed by the Society of Critical Care Medicine Thrive International Peer Support Collaborative*
McPeake, Joanne , Hirshberg, Eliotte L. , Christie, LeeAnn M., Drumright, Kelly, Hough, Catherine L. , Meyer, Joel , Wade, Dorothy , Andrews, Adair, Bakhru, Rita N. , Bates, Samantha , Barwise, John, Beesley, Sarah J. , Boehm, Leanne M. , Brown, Sheryl, Clay, Alison S. , Firshman, Penelope , Greenberg, Steven B. , Harris, Wendy, Hope, Aluko A. , Hopkins, Ramona O., Howell, David C., Jackson, James C. , Johnson, Annie, Kross, Erin K. , Lamas, Daniela, MacLeod-Smith, Belinda, Mandel, Ruth, Marshall, John C., Nackino, Megan, Quasim, Tara , Sevin, Carla M. , Slack, Andrew, Spurr, Rachel, Still, Mary, Thompson, Carol, Weinhouse, Gerald L., Wilcox, M. Elizabeth , Iwashyna, Theodore J. , Haines, Kimberley , Bastarache, Julie A. , Hill, Christopher, Hodgson, Carol Lynette , Holdsworth, Clare, Howell, David C. J., Janssen, Anna, Mikkelsen, Mark E.

Critical Care Medicine | November 13, 2018 | Volume: 47 | Issue: 1 | Pages: e21-e27

10.1097/ccm.0000000000003497 | PMID 30422863 Get It

Objectives: Patients and caregivers can experience a range of physical, psychologic, and cognitive problems following critical care discharge. The use of peer support has been proposed as an innovative support mechanism. Design: We sought to identify technical, safety, and procedural aspects of existing operational models of peer support, among the Society of Critical Care Medicine Thrive Peer Support Collaborative. We also sought to categorize key distinctions between these models and elucidate barriers and facilitators to implementation. Subjects and Setting: Seventeen Thrive sites from the United States, United Kingdom, and Australia were represented by a range of healthcare professionals. Measurements and Main Results: Via an iterative process of in-person and email/conference calls, members of the Collaborative defined the key areas on which peer support models could be defined and compared, collected detailed self-reports from all sites, reviewed the information, and identified clusters of models. Barriers and challenges to implementation of peer support models were also documented. Within the Thrive Collaborative, six general models of peer support were identified: community based, psychologist-led outpatient, models-based within ICU follow-up clinics, online, groups based within ICU, and peer mentor models. The most common barriers to implementation were recruitment to groups, personnel input and training, sustainability and funding, risk management, and measuring success. Conclusions: A number of different models of peer support are currently being developed to help patients and families recover and grow in the postcritical care setting.
Severe bleeding with subclinical oculocutaneous albinism in a patient with a novel HPS6 missense variant
Han, Chen G., O’Brien, Kevin , Coon, Lea M., Majerus, Julie A. , Huryn, Laryssa A. , Haroutunian, Sara G., Moka, Nagabhishek , Introne, Wendy J. , Macnamara, Ellen F. , Gahl, William A. , Malicdan, May Christine V. , Chen, Dong , Krishnan, Koyamangalath , Gochuico, Bernadette R. , Chen, Dong , Macnamara, Ellen

American Journal of Medical Genetics Part A | October 28, 2018 | Volume: 176 | Issue: 12 | Pages: 2819-2823

10.1002/ajmg.a.40514 | PMID 30369044 Get It

Heřmanský–Pudlák syndrome (HPS), a rare autosomal recessive disorder, manifests with oculocutaneous albinism and a bleeding diathesis. However, severity of disease can be variable and is typically related to the genetic subtype of HPS; HPS type 6 (HPS‐6) is an uncommon subtype generally associated with mild disease. A Caucasian adult female presented with a history of severe bleeding; ophthalmologic examination indicated occult oculocutaneous albinism. The patient was diagnosed with a platelet storage pool disorder, and platelet whole mount electron microscopy demonstrated absent delta granules. Genome‐wide SNP analysis showed regions of homozygosity that included the HPS1 and HPS6 genes. Full length HPS1 transcript was amplified by PCR of genomic DNA. Targeted next‐generation sequencing identified a novel homozygous missense variant in HPS6 (c.383 T > C; p.V128A); this was associated with significantly reduced HPS6 mRNA and protein expression in the patient's fibroblasts compared to control cells. These findings highlight the variable severity of disease manifestations in patients with HPS, and illustrate that HPS can be diagnosed in patients with excessive bleeding and occult oculocutaneous albinism. Genetic analysis and platelet electron microscopy are useful diagnostic tests in evaluating patients with suspected HPS.Clinical Trial registration:Registrar: ClinicalTrials.govWebsite: www.clinicaltrials.govRegistration Numbers: NCT00001456 and NCT00084305.