19 results on '"Coman DJ"'
Search Results
2. De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome.
- Author
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Chen Y, Dawes R, Kim HC, Ljungdahl A, Stenton SL, Walker S, Lord J, Lemire G, Martin-Geary AC, Ganesh VS, Ma J, Ellingford JM, Delage E, D'Souza EN, Dong S, Adams DR, Allan K, Bakshi M, Baldwin EE, Berger SI, Bernstein JA, Bhatnagar I, Blair E, Brown NJ, Burrage LC, Chapman K, Coman DJ, Compton AG, Cunningham CA, D'Souza P, Danecek P, Délot EC, Dias KR, Elias ER, Elmslie F, Evans CA, Ewans L, Ezell K, Fraser JL, Gallacher L, Genetti CA, Goriely A, Grant CL, Haack T, Higgs JE, Hinch AG, Hurles ME, Kuechler A, Lachlan KL, Lalani SR, Lecoquierre F, Leitão E, Fevre AL, Leventer RJ, Liebelt JE, Lindsay S, Lockhart PJ, Ma AS, Macnamara EF, Mansour S, Maurer TM, Mendez HR, Metcalfe K, Montgomery SB, Moosajee M, Nassogne MC, Neumann S, O'Donoghue M, O'Leary M, Palmer EE, Pattani N, Phillips J, Pitsava G, Pysar R, Rehm HL, Reuter CM, Revencu N, Riess A, Rius R, Rodan L, Roscioli T, Rosenfeld JA, Sachdev R, Shaw-Smith CJ, Simons C, Sisodiya SM, Snell P, St Clair L, Stark Z, Stewart HS, Tan TY, Tan NB, Temple SEL, Thorburn DR, Tifft CJ, Uebergang E, VanNoy GE, Vasudevan P, Vilain E, Viskochil DH, Wedd L, Wheeler MT, White SM, Wojcik M, Wolfe LA, Wolfenson Z, Wright CF, Xiao C, Zocche D, Rubenstein JL, Markenscoff-Papadimitriou E, Fica SM, Baralle D, Depienne C, MacArthur DG, Howson JMM, Sanders SJ, O'Donnell-Luria A, and Whiffin N
- Subjects
- Adolescent, Child, Child, Preschool, Female, Humans, Infant, Male, Young Adult, Alleles, Brain growth & development, Brain metabolism, Heterozygote, RNA Splice Sites genetics, Spliceosomes genetics, Syndrome, Rare Diseases genetics, Gene Expression Regulation, Developmental, Mutation, Neurodevelopmental Disorders genetics, RNA, Small Nuclear genetics
- Abstract
Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes
1 . Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2 . We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals in whom it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologues. Using RNA sequencing, we show how 5' splice-site use is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 base pair region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide., (© 2024. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF
3. Brain function in classic galactosemia, a galactosemia network (GalNet) members review.
- Author
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Panis B, Vos EN, Barić I, Bosch AM, Brouwers MCGJ, Burlina A, Cassiman D, Coman DJ, Couce ML, Das AM, Demirbas D, Empain A, Gautschi M, Grafakou O, Grunewald S, Kingma SDK, Knerr I, Leão-Teles E, Möslinger D, Murphy E, Õunap K, Pané A, Paci S, Parini R, Rivera IA, Scholl-Bürgi S, Schwartz IVD, Sdogou T, Shakerdi LA, Skouma A, Stepien KM, Treacy EP, Waisbren S, Berry GT, and Rubio-Gozalbo ME
- Abstract
Classic galactosemia (CG, OMIM #230400, ORPHA: 79,239) is a hereditary disorder of galactose metabolism that, despite treatment with galactose restriction, affects brain function in 85% of the patients. Problems with cognitive function, neuropsychological/social emotional difficulties, neurological symptoms, and abnormalities in neuroimaging and electrophysiological assessments are frequently reported in this group of patients, with an enormous individual variability. In this review, we describe the role of impaired galactose metabolism on brain dysfunction based on state of the art knowledge. Several proposed disease mechanisms are discussed, as well as the time of damage and potential treatment options. Furthermore, we combine data from longitudinal, cross-sectional and retrospective studies with the observations of specialist teams treating this disease to depict the brain disease course over time. Based on current data and insights, the majority of patients do not exhibit cognitive decline. A subset of patients, often with early onset cerebral and cerebellar volume loss, can nevertheless experience neurological worsening. While a large number of patients with CG suffer from anxiety and depression, the increased complaints about memory loss, anxiety and depression at an older age are likely multifactorial in origin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Panis, Vos, Barić, Bosch, Brouwers, Burlina, Cassiman, Coman, Couce, Das, Demirbas, Empain, Gautschi, Grafakou, Grunewald, Kingma, Knerr, Leão-Teles, Möslinger, Murphy, Õunap, Pané, Paci, Parini, Rivera, Scholl-Bürgi, Schwartz, Sdogou, Shakerdi, Skouma, Stepien, Treacy, Waisbren, Berry and Rubio-Gozalbo.)
- Published
- 2024
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4. Development of cancer surveillance guidelines in ataxia telangiectasia: A Delphi-based consensus survey of international experts.
- Author
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Neves R, De Dios Perez B, Panek R, Jagani S, Wilne S, Bhatt JM, Caputi C, Cirillo E, Coman DJ, Dückers G, Gilbert DL, Kay Koenig M, Mansour L, McDermott E, Pauni M, Pignata C, Perlman SL, Porras O, Betina Porto M, Schon K, Soler-Palacin P, Nick Russo S, Takagi M, Tischkowitz M, Wainwright C, Dandapani M, Glazebrook C, Suri M, Whitehouse WP, and Dineen RA
- Subjects
- Adult, Child, Humans, Consensus, Delphi Technique, Surveys and Questionnaires, Ataxia Telangiectasia complications, Ataxia Telangiectasia diagnosis, Neoplasms
- Abstract
Background/objectives: Ataxia telangiectasia (A-T) is a multiorgan disorder with increased vulnerability to cancer. Despite this increased cancer risk, there are no widely accepted guidelines for cancer surveillance in people affected by A-T. We aimed to understand the current international practice regarding cancer surveillance in A-T and agreed-upon approaches to develop cancer surveillance in A-T., Design/methods: We used a consensus development method, the e-Delphi technique, comprising three rounds. Round 1 consisted of a Delphi questionnaire and a survey that collected the details of respondents' professional background, experience, and current practice of cancer surveillance in A-T. Rounds 2 and 3 were designed based on previous rounds and modified according to the comments made by the panellists. The pre-specified consensus threshold was ≥75% agreement., Results: Thirty-five expert panellists from 13 countries completed the study. The survey indicated that the current practice of cancer surveillance varies widely between experts and centres'. Consensus was reached that evidence-based guidelines are needed for cancer surveillance in people with A-T, with separate recommendations for adults and children. Statements relating to the tests that should be included, the age for starting and stopping cancer surveillance and the optimal surveillance interval were also agreed upon, although in some areas, the consensus was that further research is needed., Conclusion: The international expert consensus statement confirms the need for evidence-based cancer surveillance guidelines in A-T, highlights key features that the guidelines should include, and identifies areas of uncertainty in the expert community. This elucidates current knowledge gaps and will inform the design of future clinical trials., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2023
- Full Text
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5. Metabolic Stress and Mitochondrial Dysfunction in Ataxia-Telangiectasia.
- Author
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Subramanian GN, Yeo AJ, Gatei MH, Coman DJ, and Lavin MF
- Abstract
The ataxia-telangiectasia mutated (ATM) protein kinase is, as the name implies, mutated in the human genetic disorder ataxia-telangiectasia (A-T). This protein has its "finger in many pies", being responsible for the phosphorylation of many thousands of proteins in different signaling pathways in its role in protecting the cell against a variety of different forms of stress that threaten to perturb cellular homeostasis. The classical role of ATM is the protection against DNA damage, but it is evident that it also plays a key role in maintaining cell homeostasis in the face of oxidative and other forms of non-DNA damaging stress. The presence of ATM is not only in the nucleus to cope with damage to DNA, but also in association with other organelles in the cytoplasm, which suggests a greater protective role. This review attempts to address this greater role of ATM in protecting the cell against both external and endogenous damage.
- Published
- 2022
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6. Pre-linguistic communication skill development in an infant with a diagnosis of galactosaemia.
- Author
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Lewis FM, Coman DJ, Kilcoyne S, Murdoch BE, and Syrmis M
- Subjects
- Case-Control Studies, Early Intervention, Educational, Galactosemias complications, Humans, Infant, Language Development Disorders complications, Male, Parents, Communication, Galactosemias physiopathology, Language Development, Language Development Disorders physiopathology
- Abstract
Background: Neonatal screening for galactosaemia (GAL) identifies the condition early, but subsequent biomedical and genetic testing fails to identify which subgroup of infants with GAL are at most risk of the language disorders associated with the condition. This study aims to present preliminary data on an infant with GAL based on assessment of pre-linguistic communication behaviours known to underpin language development., Methods: This single case-control study profiles the pre-linguistic skills of a 13-month-old infant with GAL. The Index Infant's performance was descriptively compared to that of a typically developing, suitably matched control infant., Results: The Index Infant was identified as presenting with clinically significant delays on 9 of the 11 pre-linguistic skills assessed., Discussion and Conclusion: The early identification of risk of developmental language difficulties in the Index Infant allows for the implementation of early intervention using the infant's parents as facilitators of language stimulation. Monitoring of the infant's progress is warranted.
- Published
- 2014
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7. Mutations in SH3PXD2B cause Borrone dermato-cardio-skeletal syndrome.
- Author
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Wilson GR, Sunley J, Smith KR, Pope K, Bromhead CJ, Fitzpatrick E, Di Rocco M, van Steensel M, Coman DJ, Leventer RJ, Delatycki MB, Amor DJ, Bahlo M, and Lockhart PJ
- Subjects
- Abnormalities, Multiple pathology, Consanguinity, Craniofacial Abnormalities pathology, Female, Humans, Limb Deformities, Congenital pathology, Male, Mitral Valve Prolapse pathology, Pedigree, Skin Abnormalities pathology, Syndrome, Abnormalities, Multiple genetics, Adaptor Proteins, Signal Transducing genetics, Mutation
- Abstract
Borrone Dermato-Cardio-Skeletal (BDCS) syndrome is a severe progressive autosomal recessive disorder characterized by coarse facies, thick skin, acne conglobata, dysmorphic facies, vertebral abnormalities and mitral valve prolapse. We identified a consanguineous kindred with a child clinically diagnosed with BDCS. Linkage analysis of this family (BDCS1) identified five regions homozygous by descent with a maximum LOD score of 1.75. Linkage analysis of the family that originally defined BDCS (BDCS3) identified an overlapping linkage peak at chromosome 5q35.1. Sequence analysis identified two different homozygous mutations in BDCS1 and BDCS3, affecting the gene encoding the protein SH3 and PX domains 2B (SH3PXD2B), which localizes to 5q35.1. Western blot analysis of patient fibroblasts derived from affected individuals in both families demonstrated complete loss of SH3PXD2B. Homozygosity mapping and sequence analysis in a second published BDCS family (BDCS2) excluded SH3PXD2B. SH3PXD2B is required for the formation of functional podosomes, and loss-of-function mutations in SH3PXD2B have recently been shown to underlie 7 of 13 families with Frank-Ter Haar syndrome (FTHS). FTHS and BDCS share some overlapping clinical features; therefore, our results demonstrate that a proportion of BDCS and FTHS cases are allelic. Mutations in other gene(s) functioning in podosome formation and regulation are likely to underlie the SH3PXD2B-mutation-negative BDSC/FTHS patients.
- Published
- 2014
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8. Fumarase deficiency in dichorionic diamniotic twins.
- Author
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Tregoning S, Salter W, Thorburn DR, Durkie M, Panayi M, Wu JY, Easterbrook A, and Coman DJ
- Subjects
- Amnion pathology, Chorion pathology, Developmental Disabilities enzymology, Diseases in Twins enzymology, Female, Humans, Infant, Newborn, Liver Diseases enzymology, Male, Pregnancy, Pregnancy, Twin, Developmental Disabilities genetics, Diseases in Twins genetics, Fumarate Hydratase deficiency, Fumarate Hydratase genetics, Liver Diseases genetics, Mutation genetics
- Abstract
Fumarase deficiency is a rare autosomal recessive inborn error of metabolism of the Krebs Tricarboxylic Acid cycle. A heavy neurological disease burden is imparted by fumarase deficiency, commonly manifesting as microcephaly, dystonia, global developmental delay, seizures, and lethality in the infantile period. Heterozygous carriers also carry an increased risk of developing hereditary leiomyomatosis and renal cell carcinoma. We describe a non-consanguineous family in whom a dichorionic diamniotic twin pregnancy resulted in twin boys with fumarase deficiency proven at the biochemical, enzymatic, and molecular levels. Their clinical phenotype included hepatic involvement. A novel mutation in the fumarate hydratase gene was identified in this family.
- Published
- 2013
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9. Charting a seven-year trajectory of language outcomes for a child with galactosemia.
- Author
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Lewis FM, Coman DJ, Syrmis M, Kilcoyne S, and Murdoch BE
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- Child, Disease Progression, Female, Galactosemias complications, Humans, Intellectual Disability diagnosis, Intellectual Disability etiology, Language Disorders etiology, Language Disorders therapy, Language Tests, Learning Disabilities diagnosis, Learning Disabilities etiology, Prospective Studies, Task Performance and Analysis, Galactosemias physiopathology, Language Development, Language Disorders diagnosis
- Abstract
Cross-sectional methodologies have revealed age-related deterioration in cognitive performance, reflecting progressive neurodegenerative change in a minority of children and adolescents with classic galactosemia (GAL). The application of longitudinal methodologies sensitive to age-related changes at the individual level is needed to determine the extent of any possible decline in function in children with GAL. The authors report on the developmental language outcomes of a 9-year-old female with GAL through an examination of her language development over a 7-year period using a performance tracking system based on the use of raw performance scores required for attainment at the 50th percentile for age. Raw scores typically increase systematically over time and are thus more sensitive to developmental changes. Results suggest that there was no decline in the child's language skills over the course of the investigation. For the case presented, the use of raw scores offered a means of examining the child's patterns of individual change, which revealed stable language skills over the period of monitoring, perhaps indicating a stable disease process for this particular child. The authors propose this descriptive application of raw performance scores that offers a means to determine neurodevelopmental outcomes in the disorder.
- Published
- 2013
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10. Differential phonological awareness skills in children with classic galactosemia: a descriptive study of four cases.
- Author
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Lewis FM, Coman DJ, Syrmis M, Kilcoyne S, and Murdoch BE
- Abstract
Educational achievement, which for individuals with the metabolic disorder classic galactosemia (GAL) is significantly lower than in the wider population, correlates with self-reported quality of life. Phonological awareness skills underpin the development of literacy, and although literacy is a key contributor to successful academic outcomes, no study to date has investigated phonological awareness skills in children with GAL. This study investigated phonological awareness (PA) in four school-aged children with the disorder, two of whom were siblings. Age range for the children was 7 years 7 months to 9 years 2 months. Each child was assessed with the Phonological Awareness criterion-referenced subtest from the Clinical Evaluation of Language Fundamentals-Fourth Edition. Included in the data for analysis was each child's performance measures obtained from their most recent assessment of cognitive and lexical development. A number of descriptive analyses were undertaken on the data. One child, who met her age criterion for PA, had cognitive and lexical development skills in the average range. The remaining three children failed to meet their age criteria. Although these three children presented with clinically similar cognitive and lexical development skills, disparate PA skills were identified. The PA skills of one of the sibling pair were notably more advanced than his older sibling. The limitations of relying on behavioural test results in children with GAL to predict those most at risk of reduced skill development are discussed in terms future research directions.
- Published
- 2013
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11. IgG N-glycans as potential biomarkers for determining galactose tolerance in Classical Galactosaemia.
- Author
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Coss KP, Byrne JC, Coman DJ, Adamczyk B, Abrahams JL, Saldova R, Brown AY, Walsh O, Hendroff U, Carolan C, Rudd PM, and Treacy EP
- Subjects
- Adult, Biomarkers, Pharmacological, Diet, Drug Tolerance, Female, Galactosemias economics, Galactosemias therapy, Glycosylation, Humans, Immunoglobulin G immunology, Male, Polysaccharides immunology, Galactose administration & dosage, Galactose metabolism, Galactosemias metabolism, Immunoglobulin G metabolism, Polysaccharides metabolism
- Abstract
N-glycan processing and assembly defects have been demonstrated in untreated and partially treated patients with Classical Galactosaemia. These defects may contribute to the ongoing pathophysiology of this disease. The aim of this study was to develop an informative method of studying differential galactose tolerance levels and diet control in individuals with Galactosaemia, compared to the standard biochemical markers. Ten Galactosaemia adults with normal intellectual outcomes were analyzed in the study. Five subjects followed galactose liberalization, increments of 300 mg to 4000 mg/day over 16 weeks, and were compared to five adult Galactosaemia controls on a galactose restricted diet. All study subjects underwent clinical and biochemical monitoring of red blood cell galactose-1-phosphate (RBC Gal-1-P) and urinary galactitol levels. Serum N-glycans were isolated and analyzed by normal phase high-performance liquid chromatography (NP-HPLC) with galactosylation of IgG used as a specific biomarker of galactose tolerance. IgG N-glycan profiles showed consistent individual alterations in response to diet liberalization. The individual profiles were improved for all, but one study subject, at a galactose intake of 1000 mg/day, with decreases in agalactosylated (G0) and increases in digalactosylated (G2) N-glycans. We conclude that IgG N-glycan profiling is an improved method of monitoring variable galactosylation and determining individual galactose tolerance in Galactosaemia compared to the standard methods., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2012
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12. Enzyme replacement therapy and extended newborn screening for mucopolysaccharidoses: opinions of treating physicians.
- Author
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Coman DJ, Hayes IM, Collins V, Sahhar M, Wraith JE, and Delatycki MB
- Abstract
We conducted a survey of physician opinions in relation to enzyme replacement therapy (ERT) and extended newborn screening (ENBS) for mucopolysaccharidoses (MPS). A questionnaire consisting of hypothetical clinical scenarios about ERT and ENBS for MPS was posted on metab-L, a list server for the metabolic community. The questionnaire included similar questions to those used in previous studies that sought the views of individuals and families affected by MPS. Our aim was to compare medical professionals' opinions with that of the individuals and families affected by MPS that they serve. The questionnaire was completed by 35 physicians, most of whom were metabolic physicians. Responses differed significantly between the physician and parent groups when the clinical scenario involved intellectual impairment. In this setting, physicians were significantly less inclined to advocate the use of ERT. Comparison of the responses to the ENBS scenarios revealed that compared to physicians, family of individuals with MPS were more inclined to desire diagnosis at birth, even if no treatment could alter the outcome of the condition. Compared to the family of individuals with MPS, physicians are more likely to advocate the use of ERT and ENBS where there is proven medical benefit to the affected individual.
- Published
- 2011
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13. Language skills in a child with Leber hereditary optic neuropathy following intrathecal chemotherapy for acute lymphoblastic leukemia.
- Author
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Lewis FM, Coman DJ, and Murdoch BE
- Subjects
- Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Humans, Injections, Spinal, Language Development Disorders diagnosis, Magnetic Resonance Imaging, Male, Optic Atrophy, Hereditary, Leber diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Antineoplastic Combined Chemotherapy Protocols adverse effects, Language Development Disorders complications, Language Development Disorders physiopathology, Optic Atrophy, Hereditary, Leber complications, Optic Atrophy, Hereditary, Leber drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
The language skills of a male child with Leber hereditary optic neuropathy (LHON) and coincidentally treated for acute lymphoblastic leukemia (ALL) with intrathecal chemotherapy at the age of 3 years 8 months were comprehensively evaluated twice over a 6-month period approximately 5½ years after diagnosis of ALL. Despite marked chemotherapy-related leukoencephalopathic changes documented on magnetic resonance imaging, the child presented with stable language skills, which were generally average to above-average based on the normative data from a comprehensive language test battery. In light of the coincidental presentation in the child of a diagnosis of LHON, which may lead to serious vision impairment and increased vulnerability to drug neurotoxicity, coupled with a history of central nervous system (CNS)-directed treatment for ALL resulting in progressive white matter pathology, the study highlights the importance of ongoing monitoring of the child's language development throughout his adolescent years.
- Published
- 2010
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14. Galactosemia, a single gene disorder with epigenetic consequences.
- Author
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Coman DJ, Murray DW, Byrne JC, Rudd PM, Bagaglia PM, Doran PD, and Treacy EP
- Subjects
- Adult, Biomarkers blood, Child, Preschool, Chromatography, High Pressure Liquid, Female, Galactosemias blood, Galactosemias complications, Galactosemias diet therapy, Gene Expression Profiling methods, Glycoproteins blood, Glycosylation, Humans, Immunoglobulin G blood, Male, Oligonucleotide Array Sequence Analysis, Polysaccharides blood, Protein Processing, Post-Translational genetics, Signal Transduction genetics, Epigenesis, Genetic, Galactosemias genetics
- Abstract
Long-term outcomes of classic galactosemia (GAL) remain disappointing. It is unclear if the complications result mainly from prenatal-neonatal toxicity or persistent glycoprotein and glycolipid synthesis abnormalities. We performed gene expression profiling (T transcriptome) to characterize key-altered genes and gene clusters of four patients with GAL with variable outcomes maintained on a galactose-restricted diet, compared with controls. Significant perturbations of multiple cell signaling pathways were observed including mitogen-activated protein kinase (MAPK) signaling, regulation of the actin cytoskeleton, focal adhesion, and ubiquitin mediated proteolysis. A number of genes significantly altered were further investigated in the GAL cohort including SPARC (osteonectin) and S100A8 (S100 calcium-binding protein). The whole serum N-glycan profile and IgG glycosylation status of 10 treated patients with GAL were compared with healthy control serum and IgG using a quantitative high-throughput analytical HPLC platform. Increased levels of agalactosylated and monogalactosylated structures and decreases in certain digalactosylated structures were identified in the patients. The persistent abnormal glycosylation of serum glycoproteins seen with the microarray data indicates persisting metabolic dyshomeostasis and gene dysregulation in "treated" GAL. Strict restriction of dietary galactose is clearly life saving in the neonatal period; long-term severe galactose restriction may contribute to ongoing systemic abnormalities.
- Published
- 2010
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15. Enzyme replacement therapy for mucopolysaccharidoses: opinions of patients and families.
- Author
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Coman DJ, Hayes IM, Collins V, Sahhar M, Wraith JE, and Delatycki MB
- Subjects
- Adult, Australia, Child, Female, Health Care Surveys, Humans, Male, Mucopolysaccharidoses psychology, Sulfatases adverse effects, Treatment Outcome, United States, Family psychology, Mucopolysaccharidoses drug therapy, Patient Acceptance of Health Care, Sulfatases therapeutic use
- Abstract
Objectives: To assess the opinions of individuals with mucopolysaccharidoses (MPS) and their parents regarding the use of enzyme replacement therapy (ERT)., Study Design: A validated questionnaire, including hypothetical clinical scenarios about ERT for MPS, was distributed to members of MPS support groups in the United States and Australia., Results: The questionnaire was completed by 249 MPS support group members. Overall, 92% were in favor of ERT where MPS causes severe physical problems but does not affect intellect, and 69% were in favor of ERT where the physical limitations are mild and intellect is spared. Only 47% were in favor of ERT where severe physical and intellectual problems are well established; however, 77% were in favor of ERT in this situation if treatment begun early prolongs life and improves quality of life., Conclusion: Most respondents were in favor of ERT for MPS, even where it would not alter the intellectual deterioration. The medical community has a responsibility to advocate for their patients in situations where ERT is appropriate and recognize the economic burden and "family function burden" ERT can incur.
- Published
- 2008
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16. Diagnostic dilemma's: the congenital disorders of glycosylation are clinical chameleons.
- Author
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Coman DJ
- Subjects
- Cutis Laxa diagnosis, Cutis Laxa genetics, Cutis Laxa metabolism, Genes, Recessive, Humans, Metabolism, Inborn Errors genetics, Metabolism, Inborn Errors metabolism, Phenotype, Glycosylation, Metabolism, Inborn Errors diagnosis
- Published
- 2008
- Full Text
- View/download PDF
17. Deletions that reveal recessive genes.
- Author
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Coman DJ and Gardner RJ
- Subjects
- Humans, Mutation, Phenotype, Chromosome Deletion, Genes, Recessive
- Published
- 2007
- Full Text
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18. Two siblings with 46,XY DSD, congenital adrenal hypoplasia, aniridia, craniofacial, and skeletal abnormalities and intrauterine growth retardation: a new syndrome?
- Author
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Coman DJ, White SM, and Amor DJ
- Subjects
- Adrenal Insufficiency genetics, Humans, Infant, Newborn, Karyotyping, Male, Syndrome, Abnormalities, Multiple genetics, Adrenal Insufficiency congenital, Aniridia genetics, Bone and Bones abnormalities, Face abnormalities, Fetal Growth Retardation genetics, Skull abnormalities
- Abstract
We report on two siblings with an unusual constellation of congenital anomalies comprising 46,XY disorder of sex development (DSD), congenital adrenal hypoplasia, aniridia, dysmorphic facial features, intrauterine growth retardation, and minor skeletal abnormalities. This combination of abnormalities is yet to be recognized in the medical literature. As such, we propose that our patients represent either a new dysmorphic syndrome or a thus far unrecognized variation of a known syndrome, such as IMAGe syndrome. The sibling recurrence suggests autosomal recessive or X-linked patterns of inheritance., ((c) 2007 Wiley-Liss, Inc.)
- Published
- 2007
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19. Seizures, ataxia, developmental delay and the general paediatrician: glucose transporter 1 deficiency syndrome.
- Author
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Coman DJ, Sinclair KG, Burke CJ, Appleton DB, Pelekanos JT, O'Neil CM, Wallace GB, Bowling FG, Wang D, De Vivo DC, and McGill JJ
- Subjects
- 3-O-Methylglucose pharmacokinetics, Anticonvulsants therapeutic use, Brain Diseases, Metabolic, Inborn diagnosis, Carbohydrate Metabolism, Inborn Errors diet therapy, Carbohydrate Metabolism, Inborn Errors etiology, Child, Diet Therapy, Female, Glucose Transporter Type 1 genetics, Humans, Infant, Lumbar Vertebrae, Male, Seizures drug therapy, Spinal Puncture, Syndrome, Treatment Outcome, Ataxia etiology, Brain Diseases, Metabolic, Inborn diet therapy, Brain Diseases, Metabolic, Inborn etiology, Developmental Disabilities etiology, Glucose Transporter Type 1 deficiency, Seizures etiology
- Abstract
Aim: Glucose transporter 1 deficiency syndrome (GLUT1-DS) is an important condition for the general paediatrician's differential armamentarium. We describe a case series of eight patients in order to raise awareness of this treatable neurometabolic condition. The diagnosis of GLUT1-DS is suggested by a decreased absolute cerebrospinal fluid (CSF) glucose value (<2.2 mmol/L) or lowered CSF: plasma glucose ratio (<0.4)., Methods: This is a review of eight Queensland patients with GLUT1-DS. The clinical presentation, clinical course, laboratory investigations and treatment outcomes are discussed., Results: The clinical features noted in our patient cohort include combinations of ataxia, developmental delay and a severe seizure disorder that is refractory to anticonvulsant medications. Seizures are the most common clinical manifestation and may be exacerbated by phenobarbitone. The paired CSF: plasma glucose results ranged from 0.2 to 0.39 (normal <0.6) with an average of 0.33. 3-O-Methyl-D-Glucose uptake and GLUT1 Genotyping analysis have been performed on five patients thus far. Rapid and impressive seizure control was observed in 100% of our patients once the ketogenic diet was instituted, with half of the cohort being able to wean completely from anticonvulsants., Conclusion: Children presenting with a clinical phenotype consisting of a refractory seizure disorder, ataxia and developmental delay should prompt the consideration of Glucose transporter 1 deficiency syndrome. While the diagnostic test of lumbar puncture is an invasive manoeuvre, the diagnosis provides a viable treatment option, the ketogenic diet. GLUT1-DS displays clinical heterogeneity, but the value of early diagnosis and treatment is demonstrated by our patient cohort.
- Published
- 2006
- Full Text
- View/download PDF
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