Results 41 to 50 of about 10,122 (170)

A Depolarizing Leak in Sodium Bicarbonate Cotransporter NBCe1 Causes Brain Edema

Annals of Clinical and Translational Neurology, EarlyView.
ABSTRACT Objectives SLC4A4 encodes electrogenic sodium bicarbonate cotransporter NBCe1, prominently expressed in kidney and brain. Recessive loss‐of‐function variants in SLC4A4 cause proximal renal tubular acidosis, no brain edema. In the brain, NBCe1 is expressed by astrocytes, where it regulates pH and mediates astrocyte volume changes.
Quinty Bisseling, Mark D. Parker, Sven Kerst, Richard A. Pasternack, Jacob Tondreau, Marjolein Breur, Gemma M. van Rooijen‐van Leeuwen, Davide Tonduti, Ettore Salsano, Alejandra Darling, Joanna A. E. van Wijk, Susanna Törnroth‐Horsefield, Marianna Bugiani, Petra J. W. Pouwels, Quinten Waisfisz, Marjo S. van der Knaap, Rogier Min   +16 more
wiley   +1 more source

Natural History of Clinical Phenotypes and Their Biochemical Correlates in Adult X-Linked Adrenoleukodystrophy. [PDF]

J Inherit Metab Dis
ABSTRACT X‐linked adrenoleukodystrophy (X‐ALD) is a rare monogenic disorder characterized by marked variability in clinical presentation, age at onset, and disease progression. A deeper understanding of its natural history and the relationship between biochemical markers and clinical phenotypes is essential for improving disease monitoring, patient ...
Lier J, Ponleitner M, Popp D, Schäfer L, Küstermann F, Meigen C, Kratzer F, Janda J, Okun J, Jamra RA, Köhler W, Bergner C.   +11 more
europepmc   +2 more sources

Genetic Diagnosis and Discovery Enabled by Large Language Models

Advanced Science, EarlyView.
We demonstrate that large language models (LLMs) can facilitate genetic diagnosis and discovery. LLMs were used to solve four types of genetic problems of sequentially increased complexity. An LLM‐based pipeline could analyze genetic variants in the genomic sequences of human hearing loss or rare genetic disease patients and assist in identifying ...
Tao Tu, Khaled Saab, Weida Liu, Zhouqing Fang, Zhuanfen Cheng, Svetolik Spasic, Maja Djurisic, Hiroaki Mohri, Wenlong Ren, Anil Palepu, Juraj Gottweis, Alan Karthikesalingam, Kavita Kulkarni, Annalisa Pawlosky, Devon Bonner, Elijah Kravets, Shruti Marwaha, Hector R. Mendez, Matthew T. Wheeler, Jonathan A. Bernstein, Undiagnosed Diseases Network, Cheng‐Yu Tsai, Chen‐Chi Wu, Konstantina M. Stankovic, Vivek Natarajan, Gary Peltz   +25 more
wiley   +1 more source

Redefining the phenotype of alpha-methylacyl-CoA racemase (AMACR) deficiency

Orphanet Journal of Rare Diseases
Background Alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare peroxisomal enzyme deficiency caused by biallelic variants in the AMACR gene. This deficiency leads to the accumulation of toxic bile acid intermediates (R)-trihydroxycholestenoic acid
Femke C.C. Klouwer, Stefan D. Roosendaal, Carla E. M. Hollak, Mirjam Langeveld, Bwee Tien Poll-The, Arlette J. van Sorge, Nicole I. Wolf, Marjo S. van der Knaap, Marc Engelen   +8 more
doaj   +1 more source

In vivo targeting of a variant causing vanishing white matter using CRISPR/Cas9

Molecular Therapy: Methods & Clinical Development, 2022
Vanishing white matter (VWM) is a leukodystrophy caused by recessive variants in subunits of eIF2B. At present, no curative treatment is available and patients often die at young age.
Anne E.J. Hillen, Martina Hruzova, Tanja Rothgangl, Marjolein Breur, Marianna Bugiani, Marjo S. van der Knaap, Gerald Schwank, Vivi M. Heine   +7 more
doaj   +1 more source

Isolated Corticospinal Tract Lesions as an Early Manifestation of Adrenoleukodystrophy in Children

Annals of the Child Neurology Society, EarlyView.
ABSTRACT Purpose X‐linked adrenoleukodystrophy (ALD) encompasses a wide range of neurological manifestations, classically described as distinct phenotypes including childhood cerebral adrenoleukodystrophy and adult‐onset adrenomyeloneuropathy (AMN).
Elle Winter, Amanda Nagy, Yedda Li, Otto Rapalino, Catherine L. Becker, Joseph Locascio, Camilo Jaimes, Florian Eichler   +7 more
wiley   +1 more source

Inactivity of Peptidase ClpP Causes Primary Accumulation of Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid Proteins, and of mtDNA

Cells, 2021
Biallelic pathogenic variants in CLPP, encoding mitochondrial matrix peptidase ClpP, cause a rare autosomal recessive condition, Perrault syndrome type 3 (PRLTS3). It is characterized by primary ovarian insufficiency and early sensorineural hearing loss,
Jana Key, Sylvia Torres-Odio, Nina C. Bach, Suzana Gispert, Gabriele Koepf, Marina Reichlmeir, A. Phillip West, Holger Prokisch, Peter Freisinger, William G. Newman, Stavit Shalev, Stephan A. Sieber, Ilka Wittig, Georg Auburger   +13 more
doaj   +1 more source

Inherited metabolic epilepsies–established diseases, new approaches

Epilepsia Open, EarlyView.
Abstract Inherited metabolic epilepsies (IMEs) represent the inherited metabolic disorders (IMDs) in which epilepsy is a prevailing component, often determining other neurodevelopmental outcomes associated with the disorder. The different metabolic pathways affected by individual IMEs are the basis of their rarity and heterogeneity.
Itay Tokatly Latzer, Phillip L. Pearl
wiley   +1 more source

White Matter Matters: A Magnetic Resonance Imaging Study with Clinical Correlates in Primary Brain Calcification

Movement Disorders, EarlyView.
Abstract Background Primary brain calcification (PBC) is a genetic disease featuring movement disorders, cognitive impairment, and/or psychiatric symptoms. Computed tomography (CT) scan identifies brain calcification but poorly correlates with patients' clinical phenotype; the role of magnetic resonance imaging (MRI) is yet undefined.
Giovanni Librizzi, Giulia Bonato, Matilde Corazza, Irene Guerra, Francesca Pistonesi, Cinzia Bertolin, Leonardo Salviati, Angelo Antonini, Renzo Manara, Miryam Carecchio   +9 more
wiley   +1 more source

Effect of Delayed Diagnosis of Phenylketonuria With Imaging Findings of Bilateral Diffuse Symmetric White Matter Lesions: A Case Report and Literature Review

Frontiers in Neurology, 2019
Phenylketonuria is a hereditary metabolic disorder due to the deficiency of tetrahydrobiopterin or phenylalanine hydroxylase. Delayed diagnoses of it manifest a progressive irreversible neurological impairment in the early years of the disease.
Shuna Chen, Mingqin Zhu, Yulei Hao, Jiachun Feng, Ying Zhang   +4 more
doaj   +1 more source