Article
Biology
Carrie E. Leonard, Jolie Quiros, Frances Lefcort, Lisa A. Taneyhill
Summary: Familial dysautonomia (FD) is a condition characterized by impaired facial pain and temperature perception, and this study reveals the role of Elp1 in the development and survival of trigeminal nociceptors. The loss of Elp1 leads to abnormal axon outgrowth and deficient target innervation, specifically affecting TrkA-expressing neurons derived from the neural crest lineage.
Article
Pediatrics
Renitha Reddi, Gabriella A. Horvath
Summary: The study aims to describe the clinical presentation of children with HSAN to pediatricians. A retrospective chart review of patients with HSAN followed in a Canadian pediatric center was performed, providing insights into clinical features, genetic etiology, and suggestions for monitoring, management, and long-term follow-up.
PAEDIATRICS & CHILD HEALTH
(2023)
Article
Medicine, General & Internal
Annette Lischka, Petra Lassuthova, Arman cakar, Christopher J. Record, Jonas Van Lent, Jonathan Baets, Maike F. Dohrn, Jan Senderek, Angelika Lampert, David L. Bennett, John N. Wood, Vincent Timmerman, Thorsten Hornemann, Michaela Auer-Grumbach, Yesim Parman, Christian A. Huebner, Miriam Elbracht, Katja Eggermann, C. Geoffrey Woods, James J. Cox, Mary M. Reilly, Ingo Kurth
Summary: This article discusses the epidemiology, pathophysiology, diagnosis and treatment of genetic pain loss disorders, which are characterized by reduced pain sensation. The development of these disorders is associated with recurrent injuries, burns and poorly healing wounds. Current treatment options mainly focus on symptomatic relief, but targeted therapies are being explored. The understanding of the genes and mechanisms related to pain loss disorders also provides new insights for the development of innovative pain medicines.
NATURE REVIEWS DISEASE PRIMERS
(2022)
Article
Clinical Neurology
Jonathan Kfir, Mengfei Wu, Mengling Liu, Leela Raju, Joel S. Schuman, Hiroshi Ishikawa, Isabel M. Vanegas, Carlos E. Mendoza-Santiesteban, Jose-Alberto Palma, Lucy Norcliffe-Kaufmann, Barr Morgenstein, Horacio Kaufmann, Gadi Wollstein
Summary: Objective Familial Dysautonomia (FD) disease lacks a useful biomarker for clinical monitoring. In this longitudinal study, structural changes in the macula, peripapillary, and optic nerve head (ONH) regions in subjects with FD were characterized. The rapidly declining RNFL and GCIPL can explain the progressive visual impairment, while ONH parameters may be most suitable for longitudinal follow-up in eyes with measurable cupping.
JOURNAL OF NEUROLOGY
(2021)
Article
Neurosciences
Matthew R. Sapio, Diana M. King, Ellen S. Staedtler, Dragan Maric, Jahandar Jahanipour, Natalya A. Kurochkina, Allison P. Manalo, Andre Ghetti, Andrew J. Mannes, Michael J. Iadarola
Summary: This study evaluates the expression pattern of a painless neuropathy gene in human tissue and finds that it is widely expressed but not enriched in pain fibers.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Clinical Neurology
Vivian Pedigone Cintra, Maike F. Dohrn, Pedro Jose Tomaselli, Fernanda Barbosa Figueiredo, Sandra Elisabete Marques, Sarah Teixeira Camargos, Luiz Sergio Mageste Barbosa, Adriana P. Rebelo, Lisa Abreu, Matt Danzi, Wilson Marques, Stephan Zuchner
Summary: Hereditary sensory neuropathies (HSN) are rare neurological disorders with heterogeneous genetic characteristics. A study conducted in Brazil identified pathogenic variants in ATL3, SPTLC2, and SCN9A genes in 12 patients from five unrelated families, contributing to a better understanding of the genetic basis of HSN.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sylvia L. Anderson, Faaria Fasih-Ahmad, Anthony J. Evans, Berish Y. Rubin
Summary: Recent research has focused on developing therapies for familial dysautonomia (FD) that facilitate the production of correct transcripts in cells and individuals with the FD-causing mutation. The study found that carnosol, a compound in rosemary, can increase the presence of correct transcripts in FD patient-derived fibroblasts by upregulating gene transcription and correcting splicing errors. Carnosol treatment also elevates the levels of two RNA-binding proteins, which promote the inclusion of specific sequences in the transcripts. These findings support the need for expedited clinical studies on the impact of carnosol on the FD patient population.
HUMAN MOLECULAR GENETICS
(2022)
Review
Genetics & Heredity
Hanrui Yu, Jie Wu, Jinju Cong, Mingxiong Chen, Yifei Huang, Jifeng Yu, Liqiang Wang
Summary: PRDM12 mutation is associated with various clinical manifestations of CIP. This study identified pain insensitivity, tongue and lip defects, and corneal ulcers as the clinical characteristics of PRDM12 mutation. The findings contribute to the diagnosis and treatment of this disease.
FRONTIERS IN GENETICS
(2023)
Review
Clinical Neurology
Alejandra Gonzalez-Duarte, Maria Cotrina-Vidal, Horacio Kaufmann, Lucy Norcliffe-Kaufmann
Summary: Familial dysautonomia (FD) is an autosomal recessive hereditary sensory and autonomic neuropathy (HSAN, type 3) that manifests at birth and leads to profound sensory loss and early death. It is caused by a founder mutation in the ELP1 gene that originated in Ashkenazi Jews and is found in 1:30 Jews of European ancestry. This mutation results in a tissue-specific skipping of exon 20 and loss of function of the ELP1 protein, which is crucial for neuronal development and survival. FD patients experience various symptoms, including blood pressure variability, dysphagia, autonomic crises, and progressive neurologic impairments. Management focuses on symptomatic and preventive measures, while disease-modifying therapies are being tested.
CLINICAL AUTONOMIC RESEARCH
(2023)
Article
Clinical Neurology
Zhongbo Chen, Reza Maroofian, A. Nazli Basak, Leena Shingavi, Mert Karakaya, Stephanie Efthymiou, Emil K. Gustavsson, Leyla Meier, Kiran Polavarapu, Seena Vengalil, Veeramani Preethish-Kumar, Bevinahalli N. Nandeesh, Nalan Gokce Gunes, Onur Akan, Fatma Candan, Bertold Schrank, Stephan Zuchner, David Murphy, Mahima Kapoor, Mina Ryten, Brunhilde Wirth, Mary M. Reilly, Atchayaram Nalini, Henry Houlden, Payam Sarraf
Summary: Pathogenic variants in PLEKHG5 have been reported in patients with autosomal recessive intermediate Charcot-Marie-Tooth disease and spinal muscular atrophy. The study identified novel biallelic variants in PLEKHG5 in 13 individuals from nine families, showing variable disease severity and age of onset. The findings suggest PLEKHG5-associated neuropathies as an important differential diagnosis in non-5q spinal muscular atrophy cases, expanding the understanding of the disease spectrum.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Museer A. Lone, Sen Zeng, Florence Bourquin, Mengli Wang, Shunxiang Huang, Zhiqiang Lin, Beisha Tang, Ruxu Zhang, Thorsten Hornemann
Summary: This study reports a novel SPTLC1p.L38R mutation in a young Chinese girl with juvenile ALS. The mutation interferes with the interaction between the protein and the regulatory ORMDL subunit of SPT, leading to increased sphingolipid synthesis, particularly dihydro-sphingolipids. These findings suggest a potential link between SPTLC1-ALS mutations and neurotoxicity.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2023)
Article
Clinical Neurology
Janel O. Johnson, Ruth Chia, Danny E. Miller, Rachel Li, Ravindran Kumaran, Yevgeniya Abramzon, Nada Alahmady, Alan E. Renton, Simon D. Topp, J. Raphael Gibbs, Mark R. Cookson, Marya S. Sabir, Clifton L. Dalgard, Claire Troakes, Ashley R. Jones, Aleksey Shatunov, Alfredo Iacoangeli, Ahmad Al Khleifat, Nicola Ticozzi, Vincenzo Silani, Cinzia Gellera, Ian P. Blair, Carol Dobson-Stone, John B. Kwok, Emily S. Bonkowski, Robin Palvadeau, Pentti J. Tienari, Karen E. Morrison, Pamela J. Shaw, Ammar Al-Chalabi, Robert H. Brown, Andrea Calvo, Gabriele Mora, Hind Al-Saif, Marc Gotkine, Fawn Leigh, Irene J. Chang, Seth J. Perlman, Ian Glass, Anna Scott, Christopher E. Shaw, A. Nazli Basak, John E. Landers, Adriano Chio, Thomas O. Crawford, Bradley N. Smith, Bryan J. Traynor
Summary: This study identified variants in the SPTLC1 gene associated with juvenile ALS, suggesting that screening for these variants may be important for patients presenting with juvenile ALS.
Article
Engineering, Biomedical
Bente E. Bloks, Lise M. Wilders, Jan Willem K. Louwerens, Alexander C. Geurts, Jorik Nonnekes, Noel L. W. Keijsers
Summary: This study aimed to understand the plantar pressure situation of patients with hereditary motor and sensory neuropathies (HMSN) and propose a quantitative outcome measure for the evaluation of surgical interventions. Plantar pressure measurements of 52 HMSN patients and 586 healthy controls were evaluated, revealing differences in plantar pressure patterns among different foot deformity categories. It was suggested to use root mean square deviations (RMSD) in combination with the fifth metatarsal head pressure ratio as outcome measures for evaluating surgical interventions in HMSN patients.
JOURNAL OF NEUROENGINEERING AND REHABILITATION
(2023)
Article
Cell & Tissue Engineering
Lior Dor, Tatiana Rabinski, Dor Zlotnik, Michal Shilian, Miguel Weil, Gad D. Vatine
Summary: This study reported the generation of induced pluripotent stem cell lines from an FD patient and his family member, retaining the disease-causing mutation and demonstrating pluripotency markers. These cell lines can differentiate into three germ layers, indicating their potential usefulness for studying FD.
STEM CELL RESEARCH
(2021)
Article
Genetics & Heredity
Jose-Alberto Palma, Rachita Yadav, Dadi Gao, Lucy Norcliffe-Kaufmann, Susan Slaugenhaupt, Horacio Kaufmann
Summary: Through whole-exome sequencing in 13 patients with congenital impaired or absent sensation to pain and temperature with no identified molecular diagnosis from a conventional genetic panel, we identified known, suspected, and likely pathogenic genetic causes of congenital insensitivity to pain in all patients, expanding the genetic landscape of congenital sensory and autonomic neuropathies. Further validation of the identified variants is needed for confirmation of their pathogenicity.
NEUROLOGY-GENETICS
(2021)