ArticleNeurology2014
PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome.
Article in Neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
PREPL in Health and Disease
Sulfamethoxazole for the Treatment of Primary PREPL Deficiency (In Dutch: Sulfamethoxazole Ter Behandeling Van Primaire PREPL deficiëntie)
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Congenital myasthenic syndromes.Orphanet journal of rare diseases · 2019Pooled it
- Presynaptic Congenital Myasthenic Syndromes.Muscle & nerve · 2026Review
- Alternative splicing and polyadenylation facilitate transcriptome diversity underlying high-altitude adaptation in pigs.Communications biology · 2026Article
- Missense variants in CMS22 patients reveal that PREPL has both enzymatic and nonenzymatic functions.JCI insight · 2024Article
- Regulators of mitonuclear balance link mitochondrial metabolism to mtDNA expression.Nature cell biology · 2023Article
- Multiomics Analyses Identify Proline Endopeptidase-Like Protein As a Key Regulator of Protein Trafficking, a Pathway Underlying Alzheimer's Disease Pathogenesis.Molecular pharmacology · 2023Article
- Prolyl Endopeptidase-like Deficiency Associated with Growth Hormone DeficiencyJournal of clinical research in pediatric endocrinology · 2023Article
- Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.International journal of molecular sciences · 2023Review
- Presynaptic Congenital Myasthenic Syndromes: Understanding Clinical Phenotypes through In vivo Models.Journal of neuromuscular diseases · 2023Review
- Prolyl endopeptidase-like is a (thio)esterase involved in mitochondrial respiratory chain function.iScience · 2021Article
- Hypotonia-cystinuria 2p21 deletion syndrome: Intrafamilial variability of clinical expression.Annals of clinical and translational neurology · 2021Article
- Clinical Application of Whole Exome Sequencing to Identify Rare but Remediable Neurologic Disorders.Journal of clinical medicine · 2020Article
- Article
- Prolyl Endopeptidase-Like Facilitates the α-Synuclein Aggregation Seeding, and This Effect Is Reverted by Serine Peptidase Inhibitor PMSF.Biomolecules · 2020Article
- [Advances in the diagnosis and treatment of congenital myasthenic syndrome].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2020Article
- First maternal uniparental disomy for chromosome 2 with PREPL novel frameshift mutation of congenital myasthenic syndrome 22 in an infant.Molecular genetics & genomic medicine · 2020Article
- PREPL Deficiency: A Homozygous Splice Site PREPL Mutation in a Patient With Congenital Myasthenic Syndrome and Absence of Ovaries and Hypoplasia of Uterus.Frontiers in genetics · 2020Article
- Amino Acid Transport Defects in Human Inherited Metabolic Disorders.International journal of molecular sciences · 2019Review
- Targeted therapies for congenital myasthenic syndromes: systematic review and steps towards a treatabolome.Emerging topics in life sciences · 2019Article
- First cardiac manifestation of hypotonia-cystinuria syndrome.Metabolic brain disease · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
objectiveTo investigate the genetic and physiologic basis of the neuromuscular symptoms of hypotonia-cystinuria syndrome (HCS) and isolated PREPL deficiency, and their response to therapy.
methodsWe performed molecular genetic, histochemical, immunoblot, and ultrastructural studies, investigated neuromuscular transmission in vitro in a patient with isolated PREPL deficiency, and evaluated the effect of pyridostigmine in this patient and in 3 patients with the HCS.
resultsHCS is caused by recessive deletions involving the SLC3A1 and PREPL genes. The major clinical features of HCS are type A cystinuria, growth hormone deficiency, muscle weakness, ptosis, and feeding problems. The proband with isolated PREPL deficiency had myasthenic symptoms since birth and a positive edrophonium test but no cystinuria. She and 1 of 3 patients with HCS responded transiently to pyridostigmine during infancy. The proband harbors a paternally inherited nonsense mutation in PREPL and a maternally inherited deletion involving both PREPL and SLC3A1; therefore, the PREPL deficiency determines the phenotype. We detected no PREPL expression in the patient's muscle and endplates. Electrophysiology studies revealed decreased quantal content of the endplate potential and reduced amplitude of the miniature endplate potential without endplate acetylcholine receptor deficiency or altered endplate geometry.
conclusionIsolated PREPL deficiency is a novel monogenic disorder that causes a congenital myasthenic syndrome with pre- and postsynaptic features and growth hormone deficiency. The myasthenic symptoms in PREPL deficiency with or without cystinuria may respond to pyridostigmine in early life. We attribute the myasthenia to abrogated interaction of PREPL with adaptor protein 1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.