Princess Royal Hospital

Abstract The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

OBJECTIVE: To review systematically the evidence for an effect of long chain and shorter chain omega 3 fatty acids on total mortality, cardiovascular events, and cancer. DATA SOURCES: Electronic databases searched to February 2002; authors contacted and bibliographies of randomised controlled trials (RCTs) checked to locate studies. REVIEW METHODS: Review of RCTs of omega 3 intake for (3) 6 months in adults (with or without risk factors for cardiovascular disease) with data on a relevant outcome. Cohort studies that estimated omega 3 intake and related this to clinical outcome during at least 6 months were also included. Application of inclusion criteria, data extraction, and quality assessments were performed independently in duplicate. RESULTS: Of 15,159 titles and abstracts assessed, 48 RCTs (36,913 participants) and 41 cohort studies were analysed. The trial results were inconsistent. The pooled estimate showed no strong evidence of reduced risk of total mortality (relative risk 0.87, 95% confidence interval 0.73 to 1.03) or combined cardiovascular events (0.95, 0.82 to 1.12) in participants taking additional omega 3 fats. The few studies at low risk of bias were more consistent, but they showed no effect of omega 3 on total mortality (0.98, 0.70 to 1.36) or cardiovascular events (1.09, 0.87 to 1.37). When data from the subgroup of studies of long chain omega 3 fats were analysed separately, total mortality (0.86, 0.70 to 1.04; 138 events) and cardiovascular events (0.93, 0.79 to 1.11) were not clearly reduced. Neither RCTs nor cohort studies suggested increased risk of cancer with a higher intake of omega 3 (trials: 1.07, 0.88 to 1.30; cohort studies: 1.02, 0.87 to 1.19), but clinically important harm could not be excluded. CONCLUSION: Long chain and shorter chain omega 3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer.

AIMS: To examine the changes in coronary, all-cause, and cancer mortality in patients with heterozygous familial hypercholesterolaemia (FH) before and after lipid-lowering therapy with statins. METHODS AND RESULTS: A total of 3382 patients (1650 men) aged <80 years were recruited from 21 lipid clinics in the United Kingdom and followed prospectively between 1980 and 2006 for 46 580 person-years. There were 370 deaths, including 190 from coronary heart disease (CHD) and 90 from cancer. The standardized mortality ratio (compared with the population in England and Wales) was calculated before and from 1 January 1992. In patients aged 20-79 years, CHD mortality fell significantly by 37% (95% CI = 7-56) from 3.4- to 2.1-fold excess. Primary prevention resulted in a 48% reduction in CHD mortality from 2.0-fold excess to none, with a smaller reduction of nearly 25% in patients with established disease. Coronary mortality was reduced more in women than in men. In patients without known CHD at registration, all-cause mortality from 1992 was 33% (21-43), lower than in the general population, mainly due to a 37% (21-50) lower risk of fatal cancer. CONCLUSION: The results emphasize the importance of early identification of FH and treatment with statins.

Abstract Objective: To assess the effect of reduction or modification of dietary fat intake on total and cardiovascular mortality and cardiovascular morbidity. Design: Systematic review. Data sources: Cochrane Library, Medline, Embase, CAB abstracts, SIGLE, CVRCT registry, and biographies were searched; trials known to experts were included. Included studies: Randomised controlled trials stating intention to reduce or modify fat or cholesterol intake in healthy adult participants over at least six months. Inclusion decisions, validity, and data extraction were duplicated. Meta-analysis (random effects methodology), meta-regression, and funnel plots were performed. Results: 27 studies (30 902 person years of observation) were included. Alteration of dietary fat intake had small effects on total mortality (rate ratio 0.98; 95% confidence interval 0.86 to 1.12). Cardiovascular mortality was reduced by 9% (0.91; 0.77 to 1.07) and cardiovascular events by 16% (0.84; 0.72 to 0.99), which was attenuated (0.86; 0.72 to 1.03) in a sensitivity analysis that excluded a trial using oily fish. Trials with at least two years' follow up provided stronger evidence of protection from cardiovascular events (0.76; 0.65 to 0.90). Conclusions: There is a small but potentially important reduction in cardiovascular risk with reduction or modification of dietary fat intake, seen particularly in trials of longer duration. What is already known on this topic The epidemiological relation between dietary fat intake and cardiovascular disease is central in strategies aimed at risk reduction in populations and individuals Systematic review of randomised controlled trials supports manipulation of dietary fat to control serum lipid concentrations, though evidence of effect on one risk factor does not rule out an opposite or reinforced effect on another unstudied risk factor Randomised controlled trials of dietary fat reduction or modification have shown varying results on cardiovascular morbidity and mortality What this study adds Systematic review of trials of modified fat intake shows that reduction or modification of dietary fat intake results in reductions in cardiovascular events, but only in trials of at least two years' duration There is little effect on total mortality Despite decades of effort and many thousands of people randomised, there is still only limited and inconclusive evidence of the effects of modification of total, saturated, monounsaturated, or polyunsaturated fats on cardiovascular morbidity and mortality

Reinke's space is a critical laryngeal structure, and the eponym remains in current use in both clinical and research settings. However, little is known about the life of the German anatomist Friedrich Berthold Reinke. His name is missing from the otolaryngological histories, despite his work on the structure he described being responsible for a fundamental advance in our understanding of the larynx. Although brilliant, Reinke was described as impetuous and coarse by his colleagues, resulting in his academic career being cut short. Reinke's relative anonymity is thought to derive from the fact that he never defined himself as a laryngologist. Without question, Reinke's observations of the human vocal fold are substantive contributions, without which modern laryngology could not have evolved. This article aimed to summarise this brilliant yet troubled man's life and achievements, allowing appreciation for his singular genius and fundamental contribution to laryngology.

after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

BACKGROUND: Thyroid peroxidase antibodies are associated with an increased risk of miscarriage and preterm birth, even when thyroid function is normal. Small trials indicate that the use of levothyroxine could reduce the incidence of such adverse outcomes. METHODS: We conducted a double-blind, placebo-controlled trial to investigate whether levothyroxine treatment would increase live-birth rates among euthyroid women who had thyroid peroxidase antibodies and a history of miscarriage or infertility. A total of 19,585 women from 49 hospitals in the United Kingdom underwent testing for thyroid peroxidase antibodies and thyroid function. We randomly assigned 952 women to receive either 50 μg once daily of levothyroxine (476 women) or placebo (476 women) before conception through the end of pregnancy. The primary outcome was live birth after at least 34 weeks of gestation. RESULTS: The follow-up rate for the primary outcome was 98.7% (940 of 952 women). A total of 266 of 470 women in the levothyroxine group (56.6%) and 274 of 470 women in the placebo group (58.3%) became pregnant. The live-birth rate was 37.4% (176 of 470 women) in the levothyroxine group and 37.9% (178 of 470 women) in the placebo group (relative risk, 0.97; 95% confidence interval [CI], 0.83 to 1.14, P = 0.74; absolute difference, -0.4 percentage points; 95% CI, -6.6 to 5.8). There were no significant between-group differences in other pregnancy outcomes, including pregnancy loss or preterm birth, or in neonatal outcomes. Serious adverse events occurred in 5.9% of women in the levothyroxine group and 3.8% in the placebo group (P = 0.14). CONCLUSIONS: The use of levothyroxine in euthyroid women with thyroid peroxidase antibodies did not result in a higher rate of live births than placebo. (Funded by the United Kingdom National Institute for Health Research; TABLET Current Controlled Trials number, ISRCTN15948785.).

BACKGROUND: Nonoperative options for osteochondral lesions (OCLs) of the talar dome are limited, and currently, there is a lack of scientific evidence to guide management. PURPOSE: To evaluate the short-term efficacy and safety of platelet-rich plasma (PRP) compared with hyaluronic acid (HA) in reducing pain and disability caused by OCLs of the ankle. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: Thirty-two patients aged 18 to 60 years were allocated to a treatment by intra-articular injections of either HA (group 1) or PRP (plasma rich in growth factors [PRGF] technique, group 2) for OCLs of the talus. Thirty OCLs, 15 per arm, received 3 consecutive intra-articular therapeutic injections and were followed for 28 weeks. The efficacy of the injections in reducing pain and improving function was assessed at each visit using the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale (AHFS); a visual analog scale (VAS) for pain, stiffness, and function; and the subjective global function score. RESULTS: The majority of patients were men (n = 23; 79%). The AHFS score improved from 66 and 68 to 78 and 92 in groups 1 and 2, respectively, from baseline to week 28 (P < .0001), favoring PRP (P < .05). Mean VAS scores (1 = asymptomatic, 10 = severe symptoms) decreased for pain (group 1: 5.6 to 3.1; group 2: 4.1 to 0.9), stiffness (group 1: 5.1 to 2.9; group 2: 5.0 to 0.8), and function (group 1: 5.8 to 3.5; group 2: 4.7 to 0.8) from baseline to week 28 (P < .0001), favoring PRP (P < .05 for stiffness, P < .01 for function, P > .05 for pain). Subjective global function scores, reported on a scale from 0 to 100 (with 100 representing healthy, preinjury function) improved from 56 and 58 at baseline to 73 and 91 by week 28 for groups 1 and 2, respectively (P < .01 in favor of PRP). CONCLUSION: Osteochondral lesions of the ankle treated with intra-articular injections of PRP and HA resulted in a decrease in pain scores and an increase in function for at least 6 months, with minimal adverse events. Platelet-rich plasma treatment led to a significantly better outcome than HA.

A woman's build, the risk of breast cancer and its subsequent prognosis seem to be related. In most but not all case-control and prospective cohort studies, an inverse relationship has been found between weight and breast cancer among premenopausal women. However, most large epidemiological studies have found that overweight or obese women are at increased risk of developing postmenopausal breast cancer. It is suggested that higher body mass index is associated with a more advanced stage of breast cancer at diagnosis in terms of tumour size but data on lymph node status is not so consistent. All treatment modalities for breast cancer such as surgery, radiotherapy, chemotherapy and hormonal treatment may be adversely affected by the presence of obesity. The overall and disease-free survival is worse in most but not all studies of prognosis of obese pre- and postmenopausal women with breast cancer.

There is widespread evidence both of the exclusion of older people from clinical research, and of under-recruitment to clinical trials. This review and opinion piece provides practical advice to assist researchers both to adopt realistic, achievable recruitment rates and to increase the number of older people taking part in research. It analyses 14 consecutive recently published trials, providing the number needed to be screened to recruit one older participant (around 3:1), numbers excluded (up to 49%), drop out rates (5-37%) and whether the planned power was achieved. The value of planning and logistics are outlined, and approaches to optimising recruitment in hospital, primary care and care home settings are discussed, together with the challenges of involving older adults with mental incapacity and those from minority groups in research. The increasingly important task of engaging older members of the public and older patients in research is also discussed. Increasing the participation of older people in research will improve the generalisability of research findings and inform best practice in the clinical management of the growing older population.

A double-blind, randomised clinical study was undertaken to compare the effect of temperature on the incidence and severity of the pain experienced on injection of propofol. The number of patients who experienced pain and the severity of the pain were reduced significantly when propofol was administered at a temperature of 4 degrees C. The efficacy of propofol as an induction agent appeared to remain unaltered.

BACKGROUND: It has been suggested that omega 3 (W3, n-3 or omega-3) fats from oily fish and plants are beneficial to health. OBJECTIVES: To assess whether dietary or supplemental omega 3 fatty acids alter total mortality, cardiovascular events or cancers using both RCT and cohort studies. SEARCH STRATEGY: Five databases including CENTRAL, MEDLINE and EMBASE were searched to February 2002. No language restrictions were applied. Bibliographies were checked and authors contacted. SELECTION CRITERIA: RCTs were included where omega 3 intake or advice was randomly allocated and unconfounded, and study duration was at least six months. Cohorts were included where a cohort was followed up for at least six months and omega 3 intake estimated. DATA COLLECTION AND ANALYSIS: Studies were assessed for inclusion, data extracted and quality assessed independently in duplicate. Random effects meta-analysis was performed separately for RCT and cohort data. MAIN RESULTS: Forty eight randomised controlled trials (36,913 participants) and 41 cohort analyses were included. Pooled trial results did not show a reduction in the risk of total mortality or combined cardiovascular events in those taking additional omega 3 fats (with significant statistical heterogeneity). Sensitivity analysis, retaining only studies at low risk of bias, reduced heterogeneity and again suggested no significant effect of omega 3 fats. Restricting analysis to trials increasing fish-based omega 3 fats, or those increasing short chain omega 3s, did not suggest significant effects on mortality or cardiovascular events in either group. Subgroup analysis by dietary advice or supplementation, baseline risk of CVD or omega 3 dose suggested no clear effects of these factors on primary outcomes. Neither RCTs nor cohorts suggested increased relative risk of cancers with higher omega 3 intake but estimates were imprecise so a clinically important effect could not be excluded. REVIEWERS' CONCLUSIONS: It is not clear that dietary or supplemental omega 3 fats alter total mortality, combined cardiovascular events or cancers in people with, or at high risk of, cardiovascular disease or in the general population. There is no evidence we should advise people to stop taking rich sources of omega 3 fats, but further high quality trials are needed to confirm suggestions of a protective effect of omega 3 fats on cardiovascular health. There is no clear evidence that omega 3 fats differ in effectiveness according to fish or plant sources, dietary or supplemental sources, dose or presence of placebo.

BACKGROUND: Actinic keratosis (AK), the most common premalignant skin condition, can represent a management challenge. Treatment should not only be effective, but also well tolerated and allow for good cosmesis on typical sun-exposed highly visible body sites. OBJECTIVES: The primary objective was to compare the lesion response and subject preference for topical methyl aminolaevulinate (MAL)-photodynamic therapy (PDT) vs. cryotherapy for the treatment of AK. METHODS: In this 24-week, multicentre, randomized, intraindividual (right-left) study, subjects received both one treatment session of MAL-PDT and a double freeze-thaw cryotherapy; the treatments were randomly allocated to either side of the face/scalp. Lesions with a noncomplete response were retreated after 12 weeks. The primary assessments were the subject's overall preference and lesion response at week 24. Secondary assessments included lesion response at week 12, cosmetic outcome, subject and investigator cosmetic outcome preference at week 24, and investigator overall preference at week 24. Skin discomfort and adverse events were also evaluated. RESULTS: In total, 119 subjects with 1,501 lesions were included in the study. At week 12, treatment with MAL-PDT resulted in a significantly larger rate of cured lesions relative to cryotherapy (percentage lesion reduction from baseline: 86.9% vs. 76.2%; P < 0.001). At week 24, both treatment groups showed a high rate of cured lesions (89.1% for MAL-PDT vs. 86.1% for cryotherapy; P = 0.20; 95% confidence interval: -1.62 to 7.67). Results for subject and investigator preferences as well as cosmetic outcome favoured MAL-PDT. Both treatment regimens were safe and well tolerated. CONCLUSIONS: The present study shows that, when treated with both MAL-PDT and cryotherapy, subjects significantly prefer MAL-PDT treatment for AK. MAL-PDT is an attractive treatment option for AK, with comparable efficacy and superior cosmetic outcomes compared with double freeze-thaw cryotherapy.

In a series of 368 incontinent women who presented to our urodynamic clinic for assessment, 232 (63%) were diagnosed as having genuine stress incontinence, and 136 (27%) as having detrusor instability. Obesity (greater than 20% more than average weight for height and age) was significantly more common in women with genuine stress incontinence and detrusor instability than in the normal population. In those with detrusor instability the body mass index was found to increase with age and parity. In women with genuine stress incontinence the body mass index increased with age and the number of previous incontinence operations; it was higher in nulliparous than in parous women. There was no significant difference between obese and nonobese women in any of the urodynamic variables measured in the two incontinence groups.

The management of chronic pain in sportsmen and women requires consideration of a wide differential diagnosis. A syndrome caused by a distension of the posterior inguinal wall is described, effectively an early direct inguinal hernia. The diagnosis can be made from certain aspects of the history and examination, which are described. The results of surgical repair to the posterior inguinal wall are excellent. The procedure was carried out on 14 sportsmen and one woman. There is an 87% return to full sporting activity, with a follow-up of 18 months to 5 years. The remaining 13% were improved by the repair. Many of the athletes had received other treatments without success. The sports hernia should be high on the list of differential diagnoses in chronic groin pain.

To assess whether embryo transfer can alter junctional zone contractility, we studied the effect of easy and difficult mock transfers in 14 oocyte donors during in-vitro fertilization (IVF) cycles. An Echovist bolus (30 microl) was used to represent embryos and transfer medium. An 'easy' transfer was judged to be an atraumatic insertion of the catheter without touching the uterine fundus. A 'difficult' embryo transfer was mimicked by deliberately touching the uterine fundus twice with the soft end of the cannula. Transvaginal scan images were recorded, digitized and converted into five times normal speed to allow us to evaluate junctional zone contractility. Easy mock embryo transfers did not change endometrial mechanical activity. Echovist remained in the upper part of the uterine cavity and was not dispersed after 45 min. A difficult procedure generated strong random waves in the fundal area and waves from fundus to cervix which relocated the Echovist in six out of seven cases. We observed movements of the transfer bolus from the upper part of the uterus towards the cervix (four cases) and into Fallopian tubes (two patients). Our study confirms that the mechanical activity of the uterus is capable of relocating intrauterine embryos and that this activity depends on physical stimulation. Junctional zone contractions can be implicated in cases of IVF/embryo transfer failure or ectopic gestation.

Abstract Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown 1 to be highly efficient for discovery of genetic associations 2 . Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group 3 . Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling ( JAK1 ), monocyte–macrophage activation and endothelial permeability ( PDE4A ), immunometabolism ( SLC2A5 and AK5 ), and host factors required for viral entry and replication ( TMPRSS2 and RAB2A ).

Lung cancer is the second commonest cancer in the UK with an incidence in 2006 of 37 100, and is the commonest cause of death from cancer, causing more than 33 000 deaths (22% of cancer deaths) each year.1 More than three-quarters of lung cancers fall into the histological category of non-small cell lung cancer (NSCLC). Currently, 10% of patients with NSCLC present with symptomatic brain metastases, and between a quarter and a third of those who initially survive radical treatment for stage III NSCLC will go on to develop brain metastases during their remaining life span.2 It is anticipated that over the next decade, an increasing proportion will develop brain metastases as adjuvant chemotherapy, concurrent chemoradiotherapy for locally advanced disease and chemotherapy for metastatic disease result in longer overall survival times. For several decades, administration of steroids followed by whole brain radiotherapy (WBRT) has been standard treatment for inoperable multiple brain metastases of any primary cancer. The duration of survival for patients with a diagnosis of multiple brain metastases is strongly influenced by their performance status and also by the presence or absence of active extracranial disease. Data from three North American clinical trials which studied dose and fractionation for WBRT were used to divide patients with brain metastases from a variety of primary sites into three prognostic subgroups using recursive partitioning analysis (RPA).3 The group identified as having the best survival were aged less than 65 years, had a Karnofsky Performance Status score ⩾70 and had controlled primary disease with no metastases outside the brain. In this group, termed RPA class I, median survival was …

Conference Abstract| February 01 2001 Mutations in the gene encoding peroxisomal α-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy S. Ferdinandusse; S. Ferdinandusse 1University of Amsterdam, Academic Medical Centre, The Netherlands. Search for other works by this author on: This Site PubMed Google Scholar S. Denis; S. Denis 1University of Amsterdam, Academic Medical Centre, The Netherlands. Search for other works by this author on: This Site PubMed Google Scholar P. T. Clayton; P. T. Clayton 3Institute of Child Health, London UK Search for other works by this author on: This Site PubMed Google Scholar A. Graham; A. Graham 4The Princes Royal Hospital, West Sussex, UK Search for other works by this author on: This Site PubMed Google Scholar J. E. Rees; J. E. Rees 4The Princes Royal Hospital, West Sussex, UK Search for other works by this author on: This Site PubMed Google Scholar J. T. Allen; J. T. Allen 5Southmead Hospital, Bristol, UK Search for other works by this author on: This Site PubMed Google Scholar B. N. McLean; B. N. McLean 6Royal Cornwall Hospital, Truro, UK Search for other works by this author on: This Site PubMed Google Scholar A. Y. Brown; A. Y. Brown 5Southmead Hospital, Bristol, UK Search for other works by this author on: This Site PubMed Google Scholar P. Vreken; P. Vreken 1University of Amsterdam, Academic Medical Centre, The Netherlands. Search for other works by this author on: This Site PubMed Google Scholar H. R. Waterham; H. R. Waterham 1University of Amsterdam, Academic Medical Centre, The Netherlands. Search for other works by this author on: This Site PubMed Google Scholar R. J. A. Wanders R. J. A. Wanders 1University of Amsterdam, Academic Medical Centre, The Netherlands. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (2001) 29 (1): A29. https://doi.org/10.1042/bst029a029c Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation S. Ferdinandusse, S. Denis, P. T. Clayton, A. Graham, J. E. Rees, J. T. Allen, B. N. McLean, A. Y. Brown, P. Vreken, H. R. Waterham, R. J. A. Wanders; Mutations in the gene encoding peroxisomal α-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy. Biochem Soc Trans 1 February 2001; 29 (1): A29. doi: https://doi.org/10.1042/bst029a029c Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 2001 Biochemical Society2001 Article PDF first page preview Close Modal You do not currently have access to this content.