David Michaeli, Ravi Rajendra, Daniel C. Kim, Michael D. Goodlett, John R. Humphries, Prasit Nimityongskul

Department of Orthopaedic Surgery, University of South Alabama, Mobile, AL, USA

Several subtypes of metaphyseal chondrodysplasia exist, of which the Schmid type is the most common. Characteristics include short limbed dwarfism, coxa vara, genu vara, and waddling gait. Skull, spine, and upper extremity involvement is minimal and often nonexistent. The primary defect involves a mutation affecting the metaphyseal portion of the growth plate, while the epiphysis is normal. A large single lineage family with metaphyseal chondrodysplasia, Schmid type (MCDS) was investigated. A genetic pedigree of 135 members of this family showed autosomal dominant inheritance between all 42 affected members. The large sample size allowed for the characterization of a broad range of features present in cases of MCDS. The majority of affected patients exhibited coxa vara with an average neck/shaft angle of 105 degrees. Despite coxa vara, premature osteoarthritis of the hip is not a feature of MCDS. Genu varum is the most prevalent knee disorder in this group, but greater than 30% of patients may exhibit genu valgum. This manuscript highlights MCDS background information, differential diagnoses, treatment options, and prognosis to aid in clinical decision-making.

DOI: 10.29245/2690-0009/2021/1.1118 View / Download Pdf

César Augusto Pinheiro Ferreira Alves1,3*, Luisa Norbert Simonsen2, Jonathan Rodrigues1, Isabella Peixoto de Barcelos2, Clarissa Bueno2, Ramon Moura Dos Santos1, Fernando Kok2,4, Leandro Tavares Lucato1

1Neuroradiology Section, Hospital das Clínicas da Universidade de São Paulo, Brazil

2Neurogenetics Unit Neurology Department, Hospital das Clínicas da Universidade de São Paulo, Brazil

3Division of Neuroradiology, Department of Radiology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

4Mendelics Genomic Analysis, São Paulo, SP, Brazil

Peroxisomal disorders are a group of expanding genetic diseases divided into two major categories: peroxisome biogenesis defects (Zellweger spectrum disorder), and single enzymatic defects. Disorders of Peroxisome Biogenesis occur when there are biallelic pathogenic variants in any of the 13 PEX genes, which code for the peroxins, proteins required for peroxisome biogenesis. This group of disorders includes two distinct phenotypes: Rhizomelic Chondrodysplasia Punctata Type-1 and Zellweger Spectrum Disorders (ZSD), of which Zellweger syndrome is the most severe, neonatal adrenoleukodystrophy is intermediate, and infantile Refsum is the mildest. The spectrum’s most frequent defects are observed in the proteins PEX1 and PEX6, and the most common clinical presentation is Zellweger spectrum, which is often associated with craniofacial dysmorphism with neurologic abnormalities. Typically, the neuroimaging pattern shows several malformative features, including a range of cortical gyral abnormalities such as microgyria and pachygyria, and impairment of the myelination. Nevertheless, we report two siblings with peroxisomal disorder, with unexpected leukodystrophy pattern of the brain mimicking lysosomal storage disease, with classical imaging features of Krabbe disease on brain magnetic resonance image.

By whole exome sequencing, we identified two pathogenic variants in compound heterozygosity in PEX6: Chr6:42.933.455 C>T (c.2435G>A), and Chr6:42.935.188 C>T (c.1802G>A). Thus, a final diagnosis of peroxisome disorder was confirmed. The index cases highlight the importance of considering peroxisome disorders as a differential diagnosis for patients with imaging features that resemble Krabbe disease.

DOI: 10.29245/2690-0009/2020/2.1117 View / Download Pdf

Loh Cheng Toa Steven1, Goh Xin Yi1*

1NTU Chinese Medicine Clinic, Nanyang Technological University, Singapore, Singapore

Chinese medicine (CM) is gaining popularity in recent years, prompting researchers’ and clinicians’ interest and effort into the makings and effects of it, especially after the announcement of World Health Organisation’s incorporation of CM into the mainstream medical compendium, followed by the promising outcome brought about by the implementation of CM in the recent pandemic. Individual herb has complex properties, coming from its pharmacological properties and the Chinese medical principles of organ-directed, taste and dynamic orientational behaviours. The use of individual herb in CM prescription is rare. Formula prescriptions predominantly consist of two ingredients or more. To fully reveal the effects of CM is a great challenge. The compound reaction of various herbs, the absorption and utility rate by the body, uniqueness of individual physique, sub-types of pathological behaviours and time-line progression at the healing process add on to the complexity of understanding the full effect of CM. Various theories such as pathophysiology guidance, pharmacokinetic-pharmacodynamic compatibility method, and Global Systems Biology for Integrative Genomics, Proteomics and Metabolomics, which interactively provide a more comprehensive and greater in-depth understanding, together with the consideration of development timeline, may shed more light to revealing the full picture of the effects of compatibility prescription.

DOI: 10.29245/2690-0009/2020/2.1116 View / Download Pdf

Jamieson B Mcdonald, Sudip Dhakal, Ian G Macreadie*

School of Science, RMIT University, Bundoora, Victoria, Australia

Alzheimer’s Disease is a highly prevalent, age-related, neurodegenerative disease associated with the accumulation of toxic proteins, including amyloid beta and tau, that affect important cellular functions. Through the study of these proteins in yeast over the past 2 decades, the effects of amyloid beta oligomerization and aggregation, and tau hyperphosphorylation on basic cellular functions, such as ageing, oxidative stress, cell cycling and proteostasis have been observed. Strategies for the prevention of damage by these proteins can be explored, thanks to the exquisite array of technologies available for yeast studies. This review summarises existing knowledge of Alzheimer’s Disease, the work over the past two decades on yeast models for Alzheimer’s Disease and how these models contribute to the development of treatments and preventative strategies for Alzheimer’s Disease.

DOI: 10.29245/2690-0009/2020/2.1114 View / Download Pdf

Marie Simone Traore1,2, Theodora M. Zohoncon1,2,3,4, Paul Ouedraogo3, Abdoul Karim Ouattara1,2, Dorcas Obiri-Yeboah5, Issoufou Tao1,2, Geoffroy Ganane1,2,3, Marius Belemgnegre3, Theodore Boro3, Fabienne Sanou3, Jacques Simpore1,2,3,4*

1Laboratory of Molecular Biology and Genetics (LABIOGENE), University Joseph KI-ZERBO, Ouagadougou, Burkina Faso

2Pietro Annigoni Biomolecular Research Center (CERBA), Ouagadougou, Burkina Faso

3Saint Camille Hospital of Ouagadougou (HOSCO), Ouagadougou, Burkina Faso

4Faculty of Medicine, University Saint Thomas d'Aquin (USTA), Ouagadougou, Burkina Faso

5Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, PMB, Cape Coast, Ghana

Introduction: The prevalence of hemoglobinopathies (HbC and HbS) is relatively high in West Africa, especially in Burkina Faso. The objectives of this study were to characterize the hematological parameters and to determine the genotypic and allelic frequencies of patients affected with hemoglobinopathies.

Methods: Hemoglobin electrophoresis was carried out in a total of 7,789 patients attending Saint Camille Hospital of Ouagadougou during the period of study. Among them, hemogram was performed for 1014 patients.

Results: The age of the study population ranged from 1 to 40 years, with a mean of 24.86 ± 12.69 years. The age group 16 to 35 were the most seen at medical center hospital and represented 3,035 out of 7,789 (38.96 %) having performed hemoglobin electrophoresis. The overall hemoglobin electrophoretic profiles revealed 223 SS, 718 SC, 2 SO-Arab, 2 AO-Arab, 3 AE, 152 CC, 799 AS, 1315 AC, and 4575 AA. The relative genotypic frequency was 58.73 % AA, 2.86 % SS and 9.22 % SC while the allelic frequencies were 0.7234 for HbA, 0.1500 for HbC, 0.1261 for HbS, 0.0002 for HbE and 0.0003 for HbO-Arab. The hemogram profiles of patients with major sickle cell syndrome (MSCS) revealed respectively for mean hemoglobin levels, number of red blood cells and mean corpuscular volume a values of 8.19 ± 1.39 g/dL ; 2.97 ± 0.73 1012/L ; 81.86 ± 12.82 fL in SS patients and 10.93 ± 1.68 g/dL ; 4.38 ± 0.77 1012/L ; 70.81 ± 7.11 fL in SC individuals.

Conclusion: The results of the present study are in line with the previous one describing the high prevalence of HbC and HbS hemoglobinopathies in Burkina Faso. Indeed, the genotypic and allelic frequencies of patients with MSCS are increasing due to the accessibility of medical care for sickle cell patients. The study diagnoses for the first-time hemoglobin AE, AO-Arab and SO-Arab genotypes in Burkina Faso.

DOI: 10.29245/2690-0009/2020/1.1109 View / Download Pdf

Marcio L.R. Souza*, Ann K. Jansen, Luiz O.C. Rodrigues, Darlene L.S. Vilela, Aline S. Martins, Juliana F. Souza, Nilton A. Rezende

Federal University of Minas Gerais, Belo Horizonte - MG, Brazil

Neurofibromatosis type 1 (NF1) is a genetic disease, characterized by multiple neural tumors as well as cutaneous symptoms. A simpler, non-invasive and cost-effective method for measuring adiposity would be useful in the care of individuals with NF1. Dual energy X-ray absorptiometry (DXA) is the standard method for this assessment but it is not widely accessible in daily clinical practice. This study aimed to compare body compositions measured using bioelectrical impedance analysis (BIA) and skinfold thickness (ST) predictive equations to those measured with DXA in twenty-six individuals with NF1. Body fat percentage (BF%) was predicted using DXA, five ST-equations and four BIA-equations. The BF% measured by DXA was 26.6 ± 7.3 and 37.4 ± 7.2 % for men and women, respectively. The best predictor of BF% was the Sun et al. BIA equation with a smaller difference compared to DXA (P=0.664), better median of adequacy (101.0%) and accuracy of 46.2%. For males, the Kyle et al. and Lohman BIA equations were the best predictors (accuracy: 78.6 and 64.3%, respectively). For females, all nine equations showed lower differences compared to DXA (P<0.001 for all equations). Among ST equations, Durnin and Womersley showed a smaller difference, greater median of adequacy and percentage of adequacy compared to DXA, even when stratified by sex. This study showed that BIA equations present better adequacy and accuracy compared to SK equations. Nevertheless, these equations should be used with caution in this population due to the variations observed in comparison to DXA.

DOI: 10.29245/2690-0009/2020/1.1112 View / Download Pdf

Marcio L.R. Souza*, Ann K. Jansen, Luiz O.C. Rodrigues, Darlene L.S. Vilela, Aline S. Martins, Juliana F. Souza, Nilton A. Rezende

Federal University of Minas Gerais, Belo Horizonte - MG, Brazil

Increased resting metabolism, by indirect calorimetry (IC), has been observed in neurofibromatosis type 1 (NF1) patients as compared to in the unaffected population. As IC is not an easily available method, the present study aimed to measure resting energy expenditure (REE) in adults with NF1 by using IC and determine the most appropriate equation to estimate the predictive value of this variable in clinical practice. Twenty-six NF1 patients aged between 18 and 45 years underwent nutritional assessment, including weight, height, and body mass index. Body composition was measured by dual energy x-ray absorptiometry (DXA). RMR was measured by IC (mREE) and by eight different equations (pREE). Statistical analysis were carried out by Kolmogorov-Smirnov test, paired student’s t test, and Bland and Altman plots. The mean age was 34.3 ± 6.1 years. The mean mREE was 1633.9 ± 471.1 kcal, and the pREE ranged from 1244.6 ± 239.9 kcal to 1519.9 ± 271.1. The best predictive REE equation for individuals with NF1 was the WHO equation (weight and height), given its small difference (although significant; P = 0.041) from the values obtained using the gold standard, good median of adequacy (92.0%), and high accuracy (46.2%). This study showed that all the eight predictive equations underestimated REE in NF1 patients (with large differences and low accuracy when compared to a gold standard method). IC is the preferred way to avoid over or underestimation of REE in NF1 patients.

DOI: 10.29245/2690-0009/2020/1.1111 View / Download Pdf

Ryan S. Funk3*, Jordan Jones2, Kishore Polireddy3, Kanecia O. Zimmerman1, Gregory Reed4, Nasreen Talib2, Mara L. Becker1

1Department of Pediatrics, Duke University Hospital, Durham, NC, USA

2Department of Pediatrics, Children’s Mercy Kansas City, Kansas City, MO, USA

3Department of Pharmacy Practice, University of Kansas, Kansas City, KS, USA

4University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, USA

Down syndrome (DS) is the most frequent genetic cause of intellectual disability and recent work has demonstrated that this population has a reduction in erythrocyte (RBC) folate concentrations, which may represent a mechanistic basis for enhanced anti-folate drug toxicity observed in these patients. In this study, folate concentrations were measured in whole blood, plasma, and RBCs in an independent cohort of children with DS (n=85); and confirms previous findings that this population has lower circulating folate concentrations compared to a control cohort consisting of juvenile arthritis patients (n=99). RBC folate concentrations were 29% lower in patients with DS, and by multivariable regression analysis reduced RBC folate concentrations were associated with: DS diagnosis (p=0.0019), lack of dietary folate supplementation (p=0.006) and female gender (p=0.03). Patients with DS supplemented with dietary folate in the form of a daily multivitamin (MVI) had 25% higher RBC folate concentrations (p=0.07), and were comparable to the RBC folate concentrations in the control cohort not receiving an MVI. However, girls with DS did not exhibit the same degree of folate repletion as boys who were supplemented with MVI.

DOI: 10.29245/2690-0009/2020/1.1110 View / Download Pdf

Rachel S. Hianik1, Mehmet A. Bilen1,2, Ragini R. Kudchadkar1,2, Margie D. Dixon1, Melinda L. Yushak1,2, Rebecca D. Pentz1,2*

1Winship Cancer Institute, USA

2Emory University School of Medicine, USA

BACKGROUND: Immunotherapy is continually being integrated into cancer care, but there is no research on communication strategies to explain it. We examine how metaphors are being used in clinical oncology to describe immunotherapy to patients.

METHODS: We observed and audio-recorded 33 first-time conversations about immunotherapy. We took note of each metaphor used in each conversation and conducted a follow-up interview to assess patient understanding of the metaphor used.

RESULTS: Metaphors were used and understanding was assessed 43 times in the 33 conversations about immunotherapy. We describe 14 metaphors used to describe four immunotherapy topics. Patients understood the metaphors 54% of the time.

CONCLUSION: Metaphors are being used by providers as a way to describe immunotherapy in clinical oncology. We hope that the examples we provide can be adapted and expanded by other oncologists to assist them in communication with patients about immunotherapy.

DOI: 10.29245/2690-0009/2019/3.1108 View / Download Pdf

Typhaine Grenet1,2, Caroline Kannengiesser3,4,5, Raphael Borie3, 5, 6, 7, Audrey Giocanti-Aurégan2

1Centre d’imagerie et de Laser, 11 rue Antoine Bourdelle, Paris, France

2Ophthalmology department, Avicenne hospital, Paris 13 University, APHP, Bobigny, France

3Université Paris Diderot, Paris, France

4Laboratoire de Génétique, APHP, Hôpital Bichat, Paris, France

5Service de Pneumologie A, Centre de Compétence des Maladies Pulmonaires Rares, Paris, France

6DHU FIRE, Hôpital Bichat, APHP, Paris, France

7INSERM, Unité 1152, Paris, France

Purpose: To report a case of bilateral Coats Plus syndrome associated with a TERT gene deletion.

Case report: A 35-year-old man with a history of liver transplant, hematological impairment, and lung fibrosis due to a TERT gene mutation was referred for blurred vision in the right eye (RE). Ophthalmological examination revealed bilateral peripheral ischemia of the retina associated with bilateral peripheral telangiectasia and telangiectasia at the posterior pole of the RE responsible for macular edema, confirmed by multimodal imaging.

Conclusion: In this young patient with bilateral Coats-like lesions associated with systemic liver and lung failures due to a TERT mutation, we report a case of Coats plus syndrome due to a TERT mutation.

DOI: 10.29245/2690-0009/2019/3.1107 View / Download Pdf

Danielle E. Hohman1, Oren S. Lerner1, Scott M. Nolan1, Grace A. Kuza1, Zakia Zaman1, Douglas B. Luckie1,2*

1Lyman Briggs College, Michigan State University, East Lansing MI, USA

2Department of Physiology, Michigan State University, East Lansing MI, USA

There are over 1,700 mutations of the CFTR gene that lead to the autosomal recessive disease cystic fibrosis (CF). Of these, the V232D mutation is a rare condition caused by a single nucleotide polymorphism at the 232nd codon. At the mutation site, a T→A nucleotide change causes GTC (valine), to become GAC (aspartic acid). This promotes the formation of non-native hydrogen bonds, which lead to a misfolding of the CFTR protein. To increase the specificity of detecting the V232D mutation of CFTR, an array of allele specific polymerase chain reaction (AS-PCR) strategies were tested. Preliminary control experiments were conducted by analyzing commercially purified genomes and human genomic DNA isolated from somatic buccal cells using chelex resin. Primers were developed to compare amplification stability versus nucleotide sequence. Applying the Yaku group’s strategy, we hypothesized that a primer designed with the V232D SNP nucleotide mismatch at the second base from the 3’ end would be more effective at diagnosing the V232D mutation of CFTR than a primer with a mismatch at the third base from the 3’ end due to steric strain principle limiting false positive results. Final analysis yielded data to support the function of our mutant seeking primers on mutant DNA. Yet further studies are needed to investigate mismatched nucleotide placement versus annealing and polymerization.

DOI: 10.29245/2690-0009/2019/2.1105 View / Download Pdf

Julie H. Andersen1,2*, Morten S. Olesen1,2

1Laboratory for Molecular Cardiology, Centre for Cardiac, Vascular, Pulmonary and Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark

2Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Through epidemiological studies, AF has been recognized to have a considerable genetic component. Genome-wide association studies have associated more than 100 genes with AF. Newer research has established a link between atrial cardiomyopathy and a predisposition for AF. This association has been further supported by recent exome and genome sequencing projects which have shown a substantial genetic overlap between genetic variants implicated in AF and cardiomyopathy in general. This review focuses on the genetic overlap between AF and cardiomyopathy.

DOI: 10.29245/2690-0009/2019/2.1106 View / Download Pdf

Yoonjeong Lim1*, Consuelo M. Kreider2, Mary Alvarez1, Roxanna M. Bendixen3

1Department of Occupational Therapy Byrdine F. Lewis College of Nursing & Health Professions, Georgia State University, Atlanta, GA, USA

2Department of Occupational Therapy, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA

3Department of Occupational Therapy, School of Health and Rehabilitation Sciences, University of Pittsburgh, Pittsburgh, PA, USA

Purpose: Barth syndrome is an X-linked rare disorder that typically affects only males. This study investigates 1) agreement between child self-reports and parent proxy-reports of HRQoL in boys with Barth syndrome and 2) relationship between parental HRQoL and parent proxy-reports of HRQoL for the child.

Materials and methods: Twenty-eight boys with Barth syndrome and their parents participated in this study. The PedsQLTM 4.0 and the PedsQLTM Family Impact Module were used to measure HRQoL of the boys, and the parents’ HRQoL, respectively. The Intraclass Correlation Coefficient was used to test agreement between the child self-reports and parent proxy-reports of HRQoL. The Spearman correlation coefficient was used to test the relationship between parental HRQoL and parent proxy-reports of HRQoL for the child.

Results: The agreement between the child self-reports and the parent proxy-reports showed moderate-to-good agreement. Higher parental HRQoL was significantly related to higher ratings of the parents on their children’s HRQoL (p < .05).

Conclusions: This study broadens understanding of HRQoL of boys with Barth syndrome using both child self-reports and parent proxy-reports. The findings indicate that the parent proxy-report of HRQoL should be used in conjunction with the child self-report when making client-centered health decisions.

DOI: 10.29245/2690-0009/2019/2.1104 View / Download Pdf

Sara Rhost1, Éamon Hughes1, Anders Ståhlberg1,2,3, Göran Landberg1,2*

1Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden

2Department of Clinical Pathology and Genetics, Sahlgrenska University Hospital, Gothenburg, Sweden

3Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden

DOI: 10.29245/2690-0009/2019/1.1103 View / Download Pdf

Hultén MA1*, Iwarsson E1, Jonasson J2

1Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden

2Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden

It is well known that most Down Syndrome cases are of maternal origin, and that the likelihood of having a child with Trisomy 21 increases with maternal age. We have now tested the possibility that the extra chromosome in Trisomy 21 Down syndrome may be due to a segregation problem, taking place during fetal mitotic oogonial cell divisions. In this context, we have analysed the chromosome constitution in 27150 pre-meiotic oogonia from 26 fetal ovarian samples with FISH technique and found that the incidence of Trisomy 21 cell nuclei is raised at later stages of fetal oogonial development. This feature can possibly explain the maternal age effect.

DOI: 10.29245/2690-0009/2019/1.1102 View / Download Pdf

Valentina Rapaccini1,2, Francesco Miconi3,4, Susanna Esposito5, Augusto Pasini1,2

1Child Neurology and Psychiatry Unit, Systems Medicine Department, University Hospital Tor Vergata, Viale Oxford 81, Rome, Italy

2Unità Sanitaria Locale (USL) Umbria 2, Viale VIII Marzo, Terni, Italy

3Paediatric Section, Università degli Studi di Perugia, Perugia, Italy

4Paediatric Clinic, Azienda Ospedaliera di Terni, Terni, Italy

5Department of Surgical and Biomedical Sciences, Paediatric Clinic, Università degli Studi di Perugia, Perugia, Italy

DOI: 10.29245/2690-0009/2019/1.1101 View / Download Pdf