Article
Ophthalmology
Obaid Imtiyazul Haque, Anbukayalvizhi Chandrasekaran, Faisal Nabi, Owais Ahmad, Joao Pedro Marques, Tanweer Ahmad
Summary: This study describes the clinical features, imaging characteristics, and genetic test results associated with a novel compound heterozygous mutation of the BEST1 gene in two siblings with autosomal recessive bestrophinopathy. The siblings presented with reduced visual acuity and bilateral subretinal deposits, and genetic testing confirmed the presence of two mutations in the BEST1 gene. Gene sequencing is an important tool for diagnosing and assessing genetic variations in this disease.
Article
Genetics & Heredity
Hae Rang Kim, Jinu Han, Yong Joon Kim, Hyun Goo Kang, Suk Ho Byeon, Sung Soo Kim, Christopher Seungkyu Lee
Summary: This study describes an observational case series of patients with ARB, revealing novel mutations in the BEST1 gene and expanding the spectrum of clinical presentations for ARB.
Article
Ophthalmology
Bo Zhao, Lian Chen, Peng Zhang, Ke He, Min Lei, Juan Zhang
Summary: This case report describes an 8-year-old female patient with both neurofibromatosis type 1 (NF1) and autosomal recessive bestrophinopathy (ARB), which have different pathogenic gene mutations. The patient presented with café-au-lait spots, freckling on skin, and characteristic findings on ophthalmological examination. Genetic testing revealed mutations in the BEST1 and NF1 genes, highlighting the importance of identifying pathogenic gene mutations for accurate diagnosis and genetic counseling.
Article
Ophthalmology
Tyler A. Pfister, Wadih M. Zein, Catherine A. Cukras, Hatice N. Sen, Ramiro S. Maldonado, Laryssa A. Huryn, Robert B. Hufnagel
Summary: This study suggests that arVMD is part of a continuum of autosomal recessive and dominant BEST1-related retinopathies, with detailed clinical and molecular assessments revealing novel variants and clinical features. Attempts to differentiate recessively and dominantly inherited BEST1-related diseases through genetic analysis did not yield significant differences.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Ophthalmology
Giuseppe Casalino, Kamron N. Khan, Monica Armengol, Genevieve Wright, Nikolas Pontikos, Michalis Georgiou, Andrew R. Webster, Anthony G. Robson, Parampal S. Grewal, Michel Michaelides
Summary: This study investigated the clinical course, genetic findings, and phenotypic spectrum of autosomal recessive bestrophinopathy (ARB). Results showed significant phenotypic heterogeneity in patients with ARB, with most patients having compound heterozygous variants and showing progressive loss of vision over time. Additionally, central retinal thickness decreased and some patients exhibited dysfunction in the rod and cone system.
Article
Genetics & Heredity
Lei Zhang, Hai-Yan Wang, Wei Jia, Ru Wang, Yu-Sheng Wang, Yang-Yang Cui
Summary: This study describes the phenotype and genotype of a patient with autosomal recessive bestrophinopathy (ARB) over a 13-year follow-up period. The patient presented with retinoschisis and cystic changes at a young age and was later diagnosed with ARB combined with secondary macular neovascularization (MNV). Genetic analyses, autofluorescence, and EOG were essential in diagnosing ARB correctly and identifying compound heterozygous BEST1 mutations.
FRONTIERS IN GENETICS
(2022)
Article
Ophthalmology
Hassan Khojasteh, Mohsen Azarmina, Nazanin Ebrahimiadib, Narsis Daftarian, Hamid Riazi-Esfahani, Houra Naraghi, Hamideh Sabbaghi, Alireza Khodabande, Hooshang Faghihi, Afrooz Moghaddasi, Fatemeh Bazvand, Masoud Reza Manaviat, Hamid Ahmadieh, Narges Hassanpoor, Fatemeh Suri
Summary: Autosomal recessive bestrophinopathy (ARB) can present with a wide spectrum of ocular abnormalities, with pachychoroid potentially being a contributing factor to angle-closure glaucoma. This study identified novel pathogenic mutations in the BEST1 gene associated with ARB.
JOURNAL OF OPHTHALMOLOGY
(2021)
Article
Ophthalmology
Feng Hu, Qian Li, Jie Shi, Ru Wang, Yongpeng Zhang, Xinyang Cao, Xin Zhang, Ya Ma, Ge Wang, Xiaoyan Peng
Summary: This study aimed to evaluate the clinical and genetic characteristics of eight members from a Chinese Han family who displayed autosomal recessive bestrophinopathy (ARB)-like retinal changes in autosomal dominant (AD) inheritance pattern. Clinical investigations and genetic analysis were performed, revealing ocular phenotypes resembling ARB in the family members. Despite the ARB-like phenotypes, a single heterozygous mutation in the BEST1 gene was detected in all eight patients, suggesting AD inheritance.
EUROPEAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Ophthalmology
Rika Yamada, Rina Takagi, Sadahiko Iwamoto, Shoichi Shimada, Akihiro Kakehashi
Summary: Autosomal recessive bestrophinopathy (ARB) is a disease caused by mutations in the BEST1 gene, with only a few mutations reported in Japanese population. This study identified a novel BEST1 mutation associated with ARB in Japanese dizygotic twins, providing significant information on genotype-phenotype association in Japanese ARB patients.
TAIWAN JOURNAL OF OPHTHALMOLOGY
(2021)
Article
Endocrinology & Metabolism
Xiuying Bai, Mark Levental, Andrew C. Karaplis
Summary: This study evaluated the safety and efficacy of burosumab in patients with ARHR1. The results showed that burosumab could normalize serum phosphate, alleviate symptoms, improve fractures and bone pain, and reduce incapacity associated with the disease. No adverse effects were reported.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Annemarie Oertli, Susanne Rinne, Robin Moss, Stefan Kaeaeb, Gunnar Seemann, Britt-Maria Beckmann, Niels Decher
Summary: KCNQ1 mutations can lead to long QT syndrome, with different forms including LQT1, RWS, and JLNS. RWS is inherited in an autosomal dominant manner, while JLNS is autosomal recessive. This study identified a rare isolated LQTS caused by an autosomal recessive KCNQ1 mutation, with asymptomatic heterozygous family members.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Natasa Dragasevic-Miskovic, Iva Stankovic, Andona Milovanovic, Vladimir S. Kostic
Summary: Autosomal recessive ataxias (ARCA) encompass a wide range of diseases, from primary ataxias to complex metabolic disorders where ataxia is just one aspect. Proper differential diagnosis is crucial for adult-onset ARCA, as they may be treatable and have prognostic implications.
JOURNAL OF NEUROLOGY
(2022)
Review
Genetics & Heredity
Thomas R. W. Nixon, Allan J. Richards, Howard Martin, Philip Alexander, Martin P. Snead
Summary: Stickler syndrome is a genetic disorder that affects the eye, ear, joints, face, and palate. It is usually inherited in a dominant manner, but can also be inherited in a recessive manner. This review of recessive Stickler syndrome cases found that high myopia and sensorineural hearing loss were common symptoms. Cleft palate was associated with certain gene variants. Retinal detachment and joint pain were also frequently reported.
Review
Biochemistry & Molecular Biology
Guendalina Bastioli, Maria Regoni, Federico Cazzaniga, Chiara Maria Giulia De Luca, Edoardo Bistaffa, Letizia Zanetti, Fabio Moda, Flavia Valtorta, Jenny Sassone
Summary: Parkinson's disease is a common neurodegenerative movement disorder characterized by the loss of dopamine neurons in the substantia nigra pars compacta. Clinical symptoms include bradykinesia, rigidity, resting tremors, and postural instability. While most cases of PD have sporadic onset, familial PD has been linked with rare genetic mutations, providing insight into the mechanism of dopamine neuron death in the disease.
Review
Biochemistry & Molecular Biology
Khaled A. Aly, Mohamed Taha Moutaoufik, Mara Zilocchi, Sadhna Phanse, Mohan Babu
Summary: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare early-onset neurodegenerative disease caused by mutations in the SACS gene. Understanding the function of Sacsin and using ARSACS disease models can improve our knowledge of this disease. Gene correction strategies and delivery methods provide hope for the development of therapeutics for ARSACS.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Rheumatology
Isabelle Melki, Herve Devilliers, Cyril Gitiaux, Vincent Bondet, Darragh Duffy, Jean-Luc Charuel, Makoto Miyara, Plamen Bokov, Ahmed Kheniche, Theresa Kwon, Francois Jerome Authier, Yves Allenbach, Alexandre Belot, Christine Bodemer, Emmanuelle Bourrat, Cecile Dumaine, Nicole Fabien, Albert Faye, Marie-Louise Fremond, Alice Hadchouel, Naoki Kitabayashi, Alice Lepelley, Maria Jose Martin-Niclos, Sasi Mudumba, Lucile Musset, Pierre Quartier, Gillian Rice, Luis Seabra, Florence Uettwiller, Carolina Uggenti, Sebastien Viel, Mathieu P. Rodero, Yanick J. Crow, Brigitte Bader-Meunier
Article
Clinical Neurology
Colin Smith, Barry W. McColl, Anirudh Patir, Jack Barrington, Jeremy Armishaw, Antonia Clarke, Jenny Eaton, Vivienne Hobbs, Sahar Mansour, Melinda Nolan, Gillian I. Rice, Mathieu P. Rodero, Luis Seabra, Carolina Uggenti, John H. Livingston, Leslie R. Bridges, Iona J. M. Jeffrey, Yanick J. Crow
ACTA NEUROPATHOLOGICA
(2020)
Article
Cell Biology
Jingshu Liu, Tal T. Sadeh, Jonathan D. Lippiat, Rajesh V. Thakker, Graeme C. Black, Forbes Manson
Summary: Dent disease type 1 is caused by mutations in the CLCN5 gene encoding CLC5, a 2Cl(-)/H+ exchanger. Two small molecules, 2-naphthoxyacetic acid (2-NOAA) and 4-phenylbutyrate (4PBA), were found to restore the function of non-Class I CLC5 mutants.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Genetics & Heredity
Carolina Uggenti, Alice Lepelley, Marine Depp, Andrew P. Badrock, Mathieu P. Rodero, Marie-Therese El-Daher, Gillian I. Rice, Somdutta Dhir, Ann P. Wheeler, Ashish Dhir, Waad Albawardi, Marie-Louise Fremond, Luis Seabra, Jennifer Doig, Natalie Blair, Maria Jose Martin-Niclos, Erika Della Mina, Alejandro Rubio-Roldan, Jose L. Garcia-Perez, Duncan Sproul, Jan Rehwinkel, Jonny Hertzog, Anne Boland-Auge, Robert Olaso, Jean-Francois Deleuze, Julien Baruteau, Karine Brochard, Jonathan Buckley, Vanessa Cavallera, Cristina Cereda, Liesbeth M. H. De Waele, Angus Dobbie, Diane Doummar, Frances Elmslie, Margarete Koch-Hogrebe, Ram Kumar, Kate Lamb, John H. Livingston, Anirban Majumdar, Charles Marques Lorenco, Simona Orcesi, Sylviane Peudenier, Kevin Rostasy, Caroline A. Salmon, Christiaan Scott, Davide Tonduti, Guy Touati, Marialuisa Valente, Helio van der Linden, Hilde Van Esch, Marie Vermelle, Kate Webb, Andrew P. Jackson, Martin A. M. Reijns, Nick Gilbert, Yanick J. Crow
Article
Biochemistry & Molecular Biology
Martin A. M. Reijns, Louise Thompson, Juan Carlos Acosta, Holly A. Black, Francisco J. Sanchez-Luque, Austin Diamond, David A. Parry, Alison Daniels, Marie O'Shea, Carolina Uggenti, Maria C. Sanchez, Alan O'Callaghan, Michelle L. L. McNab, Martyna Adamowicz, Elias T. Friman, Toby Hurd, Edward J. Jarman, Frederic Li Mow Chee, Jacqueline K. Rainger, Marion Walker, Camilla Drake, Dasa Longman, Christine Mordstein, Sophie J. Warlow, Stewart McKay, Louise Slater, Morad Ansari, Ian P. M. Tomlinson, David Moore, Nadine Wilkinson, Jill Shepherd, Kate Templeton, Ingolfur Johannessen, Christine Tait-Burkard, Jurgen G. Haas, Nick Gilbert, Ian R. Adams, Andrew P. Jackson
Review
Genetics & Heredity
Tal T. Sadeh, Graeme C. Black, Forbes Manson
Summary: Calcium channels play a crucial role in cellular functions, and mutations in the high voltage-gated calcium channel family have implications for diseases such as malignant hyperthermia, QT syndromes, deafness, and congenital stationary night blindness. Understanding the specific mechanisms of each Cav1 channel is important for developing targeted therapeutic treatments, particularly for X-linked iCSNB.
FRONTIERS IN GENETICS
(2021)
Article
Biology
Andrea Tapia, Carlo N. Giachello, Martina Palomino-Schatzlein, Richard A. Baines, Maximo Ibo Galindo
Summary: By knocking out the paralytic gene in fruit flies, researchers have developed a model that exhibits epilepsy symptoms and neuromuscular as well as cognitive alterations. Electrophysiological analyses and metabolomic profiling indicate that this model is suitable for studying the pathophysiology of Dravet syndrome and identifying potential new treatments.
Article
Immunology
Leslie Naesens, Josephine Nemegeer, Filip Roelens, Lore Vallaeys, Marije Meuwissen, Katrien Janssens, Patrick Verloo, Benson Ogunjimi, Dimitri Hemelsoet, Levi Hoste, Lisa Roels, Marieke De Bruyne, Elfride De Baere, Jo Van Dorpe, Amelie Dendooven, Anne Sieben, Gillian Rice, Tessa Kerre, Rudi Beyaert, Carolina Uggenti, Yanick J. Crow, Simon J. Tavernier, Jonathan Maelfait, Filomeen Haerynck
Summary: This study analyzed the clinical, genetic, and immunological characteristics of 3 patients with uncharacterized AGS. RNU7-1 gene mutations were found to impair the processing of RDH pre-mRNA. A distinct IFN-I signature was observed in peripheral blood, and MCP-1 (CCL2) and CXCL10 were upregulated in cerebrospinal fluid. Histopathological analysis showed thrombotic microangiopathy in kidney tissue. Dysregulated STAT phosphorylation was observed upon cytokine stimulation.
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)
Article
Neurosciences
Alex Dyson, Megan Ryan, Shruti Garg, Gareth Evans, Richard A. Baines
Summary: This study investigates the relationship between neurofibromatosis type 1 (NF1) and autism spectrum disorder (ASD) using a Drosophila model. It shows that loss of function of the NF1 gene in flies leads to tactile hypersensitivity and synaptic transmission deficits, resembling sensory abnormalities seen in individuals with ASD. The study suggests that NF1 deficiency may cause neuronal hyperexcitability and that decreased NF1 expression results in excessive neuronal firing and tactile hypersensitivity, potentially linking these two aspects. Knock-down of Ras proteins rescues both synaptic transmission deficits and behavioral deficits.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Kathleen Elverson, Jim Warwicker, Sally Freeman, Forbes Manson
Summary: Mutations in the BEST1 gene lead to the instability and loss of function of the Best1 protein, causing untreatable inherited retinal dystrophies. 4PBA and 2-NOAA have been shown to rescue the function of mutant Best1, but their therapeutic concentration is too high. A virtual docking model and screening of FDA-approved compounds identified tadalafil as a compound that can fully restore the ion channel function of a specific mutant Best1.
Correction
Multidisciplinary Sciences
Adam A. Bradlaugh, Giorgio Fedele, Anna L. Munro, Celia Napier Hansen, John M. Hares, Sanjai Patel, Charalambos P. Kyriacou, Alex R. Jones, Ezio Rosato, Richard A. Baines
Article
Multidisciplinary Sciences
Adam A. Bradlaugh, Giorgio Fedele, Anna L. Munro, Celia Napier Hansen, John M. Hares, Sanjai Patel, Charalambos P. Kyriacou, Alex R. Jones, Ezio Rosato, Richard A. Baines
Summary: Many animals, including fruit flies, use Earth's magnetic field for navigation. A study found that the C-terminal 52 amino acid residues of fruit fly CRY can facilitate magnetoreception, and increasing levels of FAD can enhance this magnetic sensitivity. These results reveal the essential components of a primary magnetoreceptor in fruit flies and suggest that non-canonical radical pairs can elicit magnetic-field responses in cells.
Article
Neurosciences
Alex Dyson, Megan Ryan, Shruti Garg, Gareth Evans, Richard A. Baines
Summary: Autism spectrum disorder (ASD) is a neurodevelopmental condition with no effective pharmacological therapies. In a study using Drosophila larvae, it was found that compounds like simvastatin and BMS-204352 could reduce tactile hypersensitivity, a symptom of ASD, but not fully rescue it.
Article
Biochemistry & Molecular Biology
Kathleen Elverson, Sally Freeman, Forbes Manson, Jim Warwicker
Summary: Many transmembrane proteins are modulated by intracellular or extracellular pH. Mutagenesis guided by amino-acid conservation and structure can be used to investigate pH dependence, but prediction of pKas can streamline this process. The hypothesis of modulation of calcium/proton coupling and pH-dependent activity through the extent of structural relaxation applies to various proteins, including bestrophin 1, TMEM16A, calmodulin, and calbindin D9k. Predicting altered pH dependence for mutations in ion channel disorders can support experimental studies and clinical intervention.
Article
Ophthalmology
Jingshu Liu, Rachel L. Taylor, Richard A. Baines, Lisa Swanton, Sally Freeman, Barbara Corneo, Achchhe Patel, Alan Marmorstein, Travis Knudsen, Graeme C. Black, Forbes Manson
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2020)