Publications by authors named "Alejandro Horga"
Objective: To analyze long-term clinical and biomarker features of anti-contactin-1 (CNTN1) autoimmune nodopathy (AN).
Methods: Patients with anti-CNTN1 autoimmune nodopathy detected in our laboratory from which clinical information was available were included. Clinical features and treatment response were retrospectively collected.
Article Synopsis
- * All affected individuals showed symptoms like muscle weakness and spasticity starting in childhood, with nerve conduction studies indicating axonal motor neuropathy.
- * Research on C. elegans mutants and potential treatment options indicates that targeted therapies might help manage RTN2-related conditions despite no significant structural changes observed in patient fibroblasts.
Article Synopsis
- Germline mutations in the DRP2 gene are linked to Charcot-Marie-Tooth disease (CMT), but the details of how these mutations cause the disease are still not fully understood.
- A study involving 9 CMT patients across 6 centers in Spain found 4 different pathogenic variants, with men showing symptoms while heterozygous women remained asymptomatic.
- The results indicate that the disease leads to late-onset sensory and motor neuropathy, characterized by lower limb weakness and nerve abnormalities including thickened nerves and fatty infiltration in muscles.
Article Synopsis
- The study investigates the impact of SARS-CoV-2 on patients with neuromuscular diseases (NMDs), aiming to identify factors that influence the severity of COVID-19 outcomes in this group.
- Researchers analyzed data from 315 patients across 13 countries, categorizing COVID-19 severity into four levels, from no hospitalization to death, and assessed various factors such as age, race, comorbidities, and baseline health status.
- Key findings showed that older age, non-White race, severe disability, respiratory dysfunction, obesity, multiple comorbidities, glucocorticoid treatment, and specific conditions like Guillain-Barré syndrome significantly raised the odds of severe COVID-19 outcomes in patients
Article Synopsis
- Functional Neurological Disorders (FND) can often occur alongside other neurological conditions, such as Creutzfeldt-Jakob disease (CJD), and may be the first signs of these underlying diseases.
- In a study of three patients, positive signs of functional movement disorders were observed before they were diagnosed with CJD, showing symptoms like unilateral tremors and limb weakness.
- The progression of their conditions was rapid, leading to significant deterioration and death within 2-3 months, emphasizing the importance of recognizing FND for proper diagnosis and management in neurology.
Article Synopsis
- LETM1 is a gene that encodes a protein in the inner mitochondrial membrane involved in regulating mitochondrial volume and ion balance, and its dysfunction is linked to various mitochondrial diseases.
- Research has discovered 18 individuals from 11 families with rare LETM1 mutations, showing severe symptoms mostly beginning in infancy, such as developmental delays, hearing loss, and neurodegeneration.
- Further studies in human cells and yeast have shown that these LETM1 mutations can lead to impaired potassium efflux and dysfunctional mitochondria, contributing to the observed neurological issues and other health problems.
Article Synopsis
- Mutations in the MRPL44 gene are linked to mitochondrial ribosome issues and have been found in patients with OXPHOS disorders and hypertrophic cardiomyopathy.
- A 23-year-old patient displayed severe myopathies and a mutation in MRPL44, suggesting a genetic cause beyond typical inheritance patterns.
- Studies show this mutation disrupts mitochondrial protein synthesis, indicating that MRPL44 defects can lead to widespread health problems, including neurological symptoms.
Article Synopsis
- * Researchers identified 32 individuals with microcephaly, neurodevelopmental issues, and other neurological symptoms due to mutations in NARS1, revealing reduced levels of NARS1 mRNA and enzyme activity in affected cells.
- * The study suggests that these mutations lead to neurodevelopmental diseases through mechanisms like toxic gain-of-function for new mutations and partial loss-of-function for recessive mutations.
Article Synopsis
- Epicrania fugax is characterized by short episodes of pain that move across the scalp or face, often in a zigzag pattern, and can radiate to other areas of the body.* -
- A study involving five women aged around 60 found that these pain episodes could start from different points on the head and quickly spread to limbs and shoulders within seconds, causing moderate to severe pain.* -
- Most patients responded well to treatments like injections or medications, suggesting that the pain's movement beyond the head may indicate underlying central nervous system involvement.*
Expanding the molecular and phenotypic spectrum of truncating mutations.
Enrico Bugiardini
,
Emanuela Bottani
,
Silvia Marchet
,
Olivia V Poole
,
Cristiane Beninca
,
Alejandro Horga
Neurol Genet
February 2020
Article Synopsis
- This study investigates the clinical effects of two truncating mutations related to mitochondrial encephalomyopathy in three patients, revealing a variety of symptoms including cerebellar ataxia, kidney issues, and cognitive decline.
- The researchers used cybrid cell studies to confirm the pathogenic nature of a novel mutation and examined how these mutations impact mitochondrial complex V structure and function.
- Findings indicate that these mutations can cause a diverse range of symptoms and display varying degrees of heteroplasmy in different tissues, emphasizing the importance of genetic counseling for affected individuals.
Article Synopsis
- Ataxia is a condition that makes people feel unbalanced and dizzy, leading to falls, and is a major reason for disability related to the nervous system.
- Researchers found a specific genetic change in a gene called RFC1 that causes a type of ataxia known as CANVAS, which affects movement and balance, especially in older people.
- In a study of 100 people with this genetic change, symptoms often started around age 60, with many experiencing a cough and balance problems, and over time, some needed walking aids or wheelchairs.
Article Synopsis
- Pyruvate dehydrogenase complex (PDC) deficiency, linked to mutations in the PDHA1 gene, shows varied symptoms in individuals, especially among heterozygous females due to X-chromosome inactivation patterns.
- This study reports two monozygotic twin females with a new missense mutation in PDHA1, who both experienced developmental delays and seizures but differed in disease severity.
- Analysis of X-chromosome inactivation revealed a significant imbalance in one twin (75:25 ratio) compared to nearly equal activity in the other (50:50), suggesting that X-inactivation may play a role in how differently the same genetic mutation affects individuals.
Article Synopsis
- The study aimed to describe the clinical features of individuals with autosomal dominant optic atrophy and cataract (ADOAC) combined with peripheral neuropathy (PN).
- Two families were evaluated, revealing common symptoms like early-onset cataracts, gastrointestinal issues, and varying types of neuropathy, including some cases of axonal neuropathy.
- Genetic analysis identified mutations related to this syndrome, suggesting that ADOAC should be considered in cases of complex inherited peripheral neuropathy, even when optic atrophy signs are not evident.
IGHMBP2 mutation associated with organ-specific autonomic dysfunction.
Neuromuscul Disord
December 2018
Article Synopsis
- Biallelic mutations in the IGHMBP2 gene lead to two conditions: spinal muscular atrophy with respiratory distress type 1 (SMARD1) and CMT2S.
- A patient experienced progressive muscle weakness and respiratory issues starting in infancy, needing 24-hour non-invasive ventilation by age 9, along with severe gastrointestinal problems.
- Genetic testing revealed a novel mutation in the IGHMBP2 gene, and the findings suggest that this disorder can cause severe nerve damage and gastrointestinal dysfunction requiring specialized nutritional support.
Article Synopsis
- Brown-Vialetto-Van Laere syndrome is a condition characterized by motor, sensory, and cranial nerve neuropathy, often along with problems like ataxia, optic atrophy, and respiratory issues that can require ventilators.
- Recent research has linked this syndrome to mutations in two riboflavin transporter genes, SLC52A2 and SLC52A3, with a study identifying 22 mutations, including 14 that were previously unknown.
- Neuropathological examinations revealed damage in the brain and spinal cord that mirrors mitochondrial disease, suggesting that impaired riboflavin transport leads to reduced mitochondrial function, which can cause neurodegenerative effects.
A de novo dominant mutation in KIF1A associated with axonal neuropathy, spasticity and autism spectrum disorder.
J Peripher Nerv Syst
December 2017
Article Synopsis
- - Mutations in the KIF1A gene can lead to various neurological disorders, with some causing hereditary sensory neuropathy and spastic paraplegia, while others result in complex conditions affecting both the central and peripheral nervous systems.
- - Researchers discovered a specific de novo missense variant (c.38G>A, p.R13H) in the KIF1A gene through exome sequencing in a patient with a unique set of symptoms.
- - This patient exhibited autism spectrum disorder (ASD), along with spastic paraplegia and axonal neuropathy, making their case distinct from other known instances of KIF1A mutations linked to neurological issues.
Article Synopsis
- * Researchers found the pathogenic c.424G>A p.Val142Ile mutation in three families of Indian ancestry, but further testing in a larger group of Indian patients did not reveal additional mutations.
- * The RNase H1 mutations are identified as a significant cause of adult mitochondrial disease related to ophthalmoplegia and other symptoms, suggesting that genetic testing for this mutation should be expanded in relevant patient groups.
Genetic and clinical characteristics of -related Charcot-Marie-Tooth disease.
J Neurol Neurosurg Psychiatry
July 2017
Article Synopsis
- The study investigates Charcot-Marie-Tooth disease (CMT) related to mutations in the neurofilament light polypeptide gene, analyzing both new patient cases and previously reported literature.
- Five new patients with specific mutations (P8R, N98S, L311P) were identified, along with common mutations found in a total of 62 families, indicating mutational hotspots responsible for significant cases.
- The findings suggest that CMT is genetically diverse, and the proposed hotspots and associations may assist in diagnosing and assessing genetic variants in CMT cases.
Article Synopsis
- * Researchers identified five mutations in noncoding regions among 25 individuals from ten families, accounting for 11.4% of diagnosed CMTX1 cases from 1996 to 2016.
- * The findings suggest that noncoding DNA mutations significantly contribute to CMTX1, emphasizing the need for future genetic testing to include these noncoding areas in inherited neuropathies.
Article Synopsis
- * Novel sequence variants (c.1168C>G and c.2209_2210del) were identified as potential causes of severe axonal neuropathy, hearing loss, and other symptoms in two siblings.
- * The pathogenicity of these mutations is supported by genetic analysis and evolutionary studies, suggesting SBF1 mutations can lead to a new form of autosomal recessive axonal neuropathy (AR-CMT2) alongside CMT4B3.
Article Synopsis
- The study focuses on a patient with distal hereditary motor neuropathy (dHMN) and lower limb spasticity, linked to a mutation in the SIGMAR1 gene.
- Whole-exome sequencing revealed a specific mutation in SIGMAR1, suggesting it as the cause of the patient's condition.
- Researchers conclude that SIGMAR1 mutations commonly lead to a combination of dHMN symptoms and suggest distinct features like upper limb extensor muscle involvement; further research is needed to confirm these findings.
Article Synopsis
- Abnormal protein aggregation is linked to various neurodegenerative diseases, specifically identified in families with axonal neuropathy due to mutations in the NEFH gene.
- These mutations lead to the production of extra amino acids that create an amyloidogenic segment, which causes toxic aggregates in cells and affects motor neurons in zebrafish models.
- Similar mechanisms were also found in other proteins associated with neurodegenerative conditions, emphasizing the need to consider the impact of stop-loss variants on protein aggregation during genetic evaluations.
Article Synopsis
- Recent research indicates that biallelic mutations in the HINT1 gene are linked to axonal neuropathy with neuromyotonia and may account for 11% of inherited neuropathies with autosomal recessive inheritance.
- A study was conducted on 152 patients with inherited neuropathies from the UK and Spain, aiming to identify HINT1 mutations, but no cases of clinical myotonia, neuromyotonia, or pathogenic mutations were found.
- The findings suggest that HINT1-related neuropathies are not evenly distributed across European populations, potentially due to founder effects, highlighting the need to consider ethnic backgrounds in genetic screening for neuropathy-related mutations.
Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles.
Belén de la Hera
,
Elena Urcelay
,
David Brassat
,
Andrew Chan
,
Angela Vidal-Jordana
,
Alejandro Horga
Neurol Neuroimmunol Neuroinflamm
December 2014
Article Synopsis
- The study investigated the link between HLA class I and II alleles and the occurrence of anaphylactic or anaphylactoid reactions in multiple sclerosis (MS) patients receiving natalizumab treatment.
- Genotyping was conducted on 119 MS patients, with 54 having allergic reactions and 65 not, revealing significant associations of specific HLA-DRB1 alleles with these reactions.
- Findings suggest that HLA-DRB1 genotyping could be a useful tool for neurologists to identify MS patients at risk for severe allergic reactions to natalizumab.