Author
Tony Huynh
Other affiliations: University of Queensland, Australian National University, Children's National Medical Center
Bio: Tony Huynh is an academic researcher from Boston Children's Hospital. The author has contributed to research in topics: Medicine & Type 1 diabetes. The author has an hindex of 11, co-authored 28 publications receiving 598 citations. Previous affiliations of Tony Huynh include University of Queensland & Australian National University.
Papers
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University of Melbourne1, Boston Children's Hospital2, Royal Children's Hospital3, Monash Medical Centre4, Monash University5, Monash University, Clayton campus6, Children's Hospital at Westmead7, University of New South Wales8, University of Sydney9, Royal Prince Alfred Hospital10, Australian National University11, University of Western Australia12, Diabetes Australia13, King Edward Memorial Hospital14, University of Adelaide15, University of Otago16, Christchurch Hospital17, University of Auckland18, University of Florence19, University of Groningen20, Erasmus University Rotterdam21, Medical University of Vienna22, Ghent University Hospital23, University of Manitoba24, Diponegoro University25, Hudson Institute of Medical Research26, University of Queensland27
TL;DR: A massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously and expands the understanding of the underlying genetic etiology of DSD.
Abstract: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46,XY DSD and 48 with 46,XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46,XY DSD. In patients with 46,XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management. Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes.
221 citations
TL;DR: Successful improvement of dystrophy independent of hormonal, growth, or immunosuppressive effects is demonstrated, indicating VBP15 merits clinical investigation for DMD and would benefit other chronic inflammatory diseases.
Abstract: Absence of dystrophin makes skeletal muscle more susceptible to injury, resulting in breaches of the plasma membrane and chronic inflammation in Duchenne muscular dystrophy (DMD). Current management by glucocorticoids has unclear molecular benefits and harsh side effects. It is uncertain whether therapies that avoid hormonal stunting of growth and development, and/or immunosuppression, would be more or less beneficial. Here, we discover an oral drug with mechanisms that provide efficacy through anti-inflammatory signaling and membrane-stabilizing pathways, independent of hormonal or immunosuppressive effects. We find VBP15 protects and promotes efficient repair of skeletal muscle cells upon laser injury, in opposition to prednisolone. Potent inhibition of NF-κB is mediated through protein interactions of the glucocorticoid receptor, however VBP15 shows significantly reduced hormonal receptor transcriptional activity. The translation of these drug mechanisms into DMD model mice improves muscle strength, live-imaging and pathology through both preventive and post-onset intervention regimens. These data demonstrate successful improvement of dystrophy independent of hormonal, growth, or immunosuppressive effects, indicating VBP15 merits clinical investigation for DMD and would benefit other chronic inflammatory diseases.
151 citations
01 May 2009
TL;DR: Although the majority of diabetes mellitus in youth remains type 1 and the incidence of type 2 is rising, MODY should be considered in patients with non-ketotic diabetes at presentation, and in patientsWith a strong family history of diabetes Mellitus without pancreatic auto-antibodies, the diagnosis must be confirmed by molecular studies.
Abstract: Maturity Onset Diabetes of Young (MODY) is a monogenic and autosomal dominant form of diabetes mellitus with onset of the disease often before 25 years of age. It is due to dysfunction of pancreatic beta cells characterised by non-ketotic diabetes and absence of pancreatic auto-antibodies. It is frequently mistaken for type 1 or type 2 diabetes mellitus. Diagnosis of MODY is important as the GCK subtype has better prognosis and may not require any treatment. Subtypes HNF1A and HNF4A are sensitive to sulfonylureas, however diabetes complications are common if not treated early. Moreover, there is genetic implication for the patient and family. Rare MODY subtypes can be associated with pancreatic and renal anomalies as well as exocrine dysfunction of the pancreas. So far there are six widely accepted subtypes of MODY described but the list has grown to nine. Although the majority of diabetes mellitus in youth remains type 1 and the incidence of type 2 is rising, MODY should be considered in patients with non-ketotic diabetes at presentation, and in patients with a strong family history of diabetes mellitus without pancreatic auto-antibodies. Furthermore the diagnosis must be confirmed by molecular studies. With advancement in genomic technology, rapid screening for MODY mutations will become readily available in the future.
56 citations
01 May 2009
TL;DR: A greater understanding of the genotype-phenotype correlation supports the view that 21-OH Deficiency is a continuum of phenotypes as opposed to a number of distinct phenotypical entities.
Abstract: 21-Hydroxylase Deficiency (21-OH Deficiency) represents the most common form of Congenital Adrenal Hyperplasia (CAH), a complex and heterogenous group of conditions, characterised by defects in one of the five enzymes involved in adrenal steroidogenesis. Defects in this steroidogenic enzyme, the product of the CYP21A2 gene, cause disruption in the pathway involved in cortisol and aldosterone production and consequently, the accumulation of their steroid precursors as well as a resulting adrenocorticotrophic hormone (ACTH)-driven overproduction of adrenal androgens. Treatment with glucocorticoid, with or without mineralocorticoid and salt replacement, is directed at preventing adrenal crises and ensuring normal childhood growth by alleviating hyperandrogenism. Conventionally, two clinical forms of 21-OH Deficiency are described - the classical form, separated into salt-wasting and simple-virilising phenotypes, and the non-classical form. They are differentiated by their hormonal profile, predominant clinical features and age of presentation. A greater understanding of the genotype-phenotype correlation supports the view that 21-OH Deficiency is a continuum of phenotypes as opposed to a number of distinct phenotypical entities. Significant advancements in technologies such as Tandem Mass Spectrometry (TMS) and improvements in gene analysis, such as complete PCR-based sequencing of the involved gene, have resulted in remarkable developments in the areas of diagnosis, treatment and treatment monitoring, neonatal screening, prenatal diagnosis and prenatal therapy.
47 citations
Erasmus University Rotterdam1, Dokuz Eylül University2, Cambridge University Hospitals NHS Foundation Trust3, Children's Hospital of Eastern Ontario4, University of Louisville5, Carol Davila University of Medicine and Pharmacy6, Boston Children's Hospital7, University of Naples Federico II8, VU University Amsterdam9, University of Cambridge10, Sheffield Hallam University11, Vita-Salute San Raffaele University12, University of Plymouth13, St. John's Medical College14, Queen Mary University of London15, Barts Health NHS Trust16, Semmelweis University17, University of Queensland18, Gdańsk Medical University19, Radboud University Nijmegen20, Charité21, MultiCare Health System22, Charles University in Prague23, Universidade Federal de Pelotas24, Estácio S.A.25, University Medical Center Groningen26, Children's Hospital of Philadelphia27, University of Chile28, University of Debrecen29, Christian Medical College & Hospital30, University of Turin31, Services Hospital32, Marmara University33, Royal Children's Hospital34, university of lille35, University of Freiburg36, University of Regensburg37, Hebrew University of Jerusalem38, Kaplan Medical Center39, University of Amsterdam40
TL;DR: The few motor and cognitive abilities of patients did not improve with age, as evidenced by the absence of significant correlations between biological age and scores on the Gross Motor Function Measure-88 and Bayley Scales of Infant Development III.
42 citations
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TL;DR: It is suggested that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units, outpatients, and referrals to social services, but for house doctors to assess overdoses would provide no economy for the psychiatric or social services.
Abstract: admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER
4,497 citations
TL;DR: Prader-Willi syndrome is characterized by severe infantile hypotonia with poor suck and failure to thrive; hypogonadism causing genital hypoplasia and pubertal insufficiency; characteristic facial features; early-childhood onset obesity and hyperphagia; developmental delay/mild intellectual disability; short stature; and a distinctive behavioral phenotype.
1,353 citations
The American College of Financial Services1, Icahn School of Medicine at Mount Sinai2, Wayne State University3, Emory University4, Cleveland Clinic5, University of California, San Diego6, Ochsner Medical Center7, Louisiana State University8, University of Tennessee Health Science Center9, University of Texas at Dallas10, American Association of Clinical Endocrinologists11, Harvard University12, Baylor College of Medicine13, University of Alabama at Birmingham14, Veterans Health Administration15, University of Washington16, Mayo Clinic17, University of Miami18, University of California, Santa Barbara19, SUNY Downstate Medical Center20, University of Arizona21, Washington University in St. Louis22, University of Southern California23, University of California, Los Angeles24, University of California, Irvine25, Eastern Virginia Medical School26, Cornell University27
TL;DR: These guidelines are a working document that reflects the state of the field at the time of publication and any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances.
634 citations
534 citations
Université de Montréal1, Karolinska Institutet2, University of Wisconsin-Madison3, Paul Sabatier University4, Aarhus University5, University of Sydney6, Université catholique de Louvain7, University of Toronto8, Harvard University9, University of Kansas10, University of California, Berkeley11, University of California, Los Angeles12, University of New South Wales13, Imperial College London14, Erasmus University Rotterdam15, University of Gothenburg16, Duke University17, Ohio University18, National Institutes of Health19, University of Florida20, New York Medical College21, French Institute of Health and Medical Research22, University of Pittsburgh23, Rutgers University24, University of Kentucky25, University of Helsinki26, McMaster University27, University of Queensland28
TL;DR: Following a multidisciplinary evaluation, preferably by experts, rhGH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental, and lifestyle interventions.
Abstract: Context: Recombinant human GH (rhGH) therapy in Prader-Willi syndrome (PWS) has been used by the medical community and advocated by parental support groups since its approval in the United States in 2000 and in Europe in 2001. Its use in PWS represents a unique therapeutic challenge that includes treating individuals with cognitive disability, varied therapeutic goals that are not focused exclusively on increased height, and concerns about potential life-threatening adverse events. Objective: The aim of the study was to formulate recommendations for the use of rhGH in children and adult patients with PWS. Evidence: We performed a systematic review of the clinical evidence in the pediatric population, including randomized controlled trials, comparative observational studies, and long-term studies (>3.5 y). Adult studies included randomized controlled trials of rhGH treatment for ≥6 months and uncontrolled trials. Safety data were obtained from case reports, clinical trials, and pharmaceutical registries. Methodology: Forty-three international experts and stakeholders followed clinical practice guideline development recommendations outlined by the AGREE Collaboration (www.agreetrust.org). Evidence was synthesized and graded using a comprehensive multicriteria methodology (EVIDEM) (http://bit.ly.PWGHIN). Conclusions: Following a multidisciplinary evaluation, preferably by experts, rhGH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental, and lifestyle interventions. Cognitive impairment should not be a barrier to treatment, and informed consent/assent should include benefit/risk information. Exclusion criteria should include severe obesity, uncontrolled diabetes mellitus, untreated severe obstructive sleep apnea, active cancer, or psychosis. Clinical outcome priorities should vary depending upon age and the presence of physical, mental, and social disability, and treatment should be continued for as long as demonstrated benefits outweigh the risks. Copyright
275 citations