Late-onset Disorder Research Articles

Consanguineous couples' experiences and views regarding expanded carrier screening: Barriers and facilitators in the decision-making process.

Expanded carrier screening (ECS) entails a screening offer for multiple recessive disorders at the same time, and allows testing of individuals or couples regardless of ancestry or geographic origin. Children of consanguineous couples have a higher-than-average risk of manifesting autosomal recessive disorders. This study aims to contribute to the responsible implementation of ECS for consanguineous couples. Seven semi-structured interviews were conducted with consanguineous couples who had recently participated in Whole Exome Sequencing (WES)-based ECS at Maastricht University Medical Center (MUMC+), the Netherlands. The test offered at MUMC+ covers a large number of disease-related genes (~2000), including severe, relatively mild, early- and late-onset disorders. Respondents were interviewed about their views on, and experiences with participation in WES-based ECS. Overall, participation was experienced as worthwhile: it enabled respondents to make informed choices with regard to family planning as well as to take on the presumed parental responsibility to deliver their children as healthy as possible. Furthermore, our findings suggest that (1) true consent for having this test requires timely information about the possible implications of a positive test result for specific categories of findings, as well as about the success rates of the available reproductive options; (2) the clinical geneticist can play a pivotal part in informing participants as well as providing clear information about autosomal recessive inheritance; (3) more research is needed to explore what type of genetic risk information is considered 'meaningful' by participants and actually contributes to reproductive decision-making.

Síndrome de temblor y ataxia asociado a frágil X (FXTAS): revisión de la literatura

El síndrome de temblor y ataxia asociado al síndrome del cromosoma X frágil (FXTAS) es un desorden neurodegenerativo progresivo (1), de inicio tardío, que ocurre entre los portadores de la premutación del gen FMR1 (Fragile X Mental Retardation 1), el cual está estrechamente asociado con el síndrome del cromosoma X frágil (FXS). El FXTAS se caracteriza por déficits neurológicos que incluyen temblor de intención progresivo, ataxia cerebelosa, parkinsonismo, neuropatía periférica, déficits cognitivos y disfunción autonómica (2-4).
 El FXTAS surge como una importante opción diagnóstica en hombres con temblor, alteraciones en la marcha y síntomas neurodegenerativos. En general existe subregistro de esta patología dado que es un síndrome recientemente descrito y falta conocimiento de los profesionales de salud al respecto, los cuales, debido a la similitud de su presentación clínica con otros desórdenes neurológicos, generalmente suelen confundir el diagnóstico (5).
 En Colombia no se ha documentado la prevalencia de SXF o de FXTAS. Sin embargo, se ha descrito un corregimiento en el Valle del Cauca que tiene una prevalencia de más de cien veces lo reportado en la literatura de SFX, lo que nos sugiere que en Colombia existe subregistro del SFX y de FXTAS.
 Esta revisión tiene por objeto difundir los avances del conocimiento de las manifestaciones clínicas, la neurofisiopatología y las posibilidades de tratamiento de los pacientes con FXTAS, y así aumentar diagnóstico y aportar a mejorar la calidad de vida de los afectados y de sus familias.

Dysregulation of DNA repair genes in Fuchs endothelial corneal dystrophy

Fuchs Endothelial Corneal Dystrophy (FECD), a late-onset oxidative stress disorder, is the most common cause of corneal endothelial degeneration and is genetically associated with CTG repeat expansion in Transcription Factor 4 (TCF4). We previously reported accumulation of nuclear (nDNA) and mitochondrial (mtDNA) damage in FECD. Specifically, mtDNA damage was a prominent finding in development of disease in the ultraviolet-A (UVA) induced FECD mouse model. We hypothesize that an aberrant DNA repair may contribute to the increased DNA damage seen in FECD. We analyzed differential expression profiles of 84 DNA repair genes by real-time PCR arrays using Human DNA Repair RT-Profiler plates using cDNA extracted from Descemet's membrane-corneal endothelium (DM-CE) obtained from FECD patients with expanded (>40) or non-expanded (<40) intronic CTG repeats in TCF4 gene and from age-matched normal donors. Change in mRNA expression of <0.5- or >2.0-fold in FECD relative to normal was set as cutoff for down- or upregulation. Downregulated mitochondrial genes were further validated using the UVA-based mouse model of FECD. FECD specimens exhibited downregulation of 9 genes and upregulation of 8 genes belonging to the four major DNA repair pathways, namely, base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), and double strand break (DSB) repair, compared to normal donors. MMR gene MSH2 and BER gene POLB were preferentially upregulated in expanded FECD. BER genes LIG3 and NEIL2, DSB repair genes PARP3 and TOP3A, NER gene XPC, and unclassified pathway gene TREX1, were downregulated in both expanded and non-expanded FECD. MtDNA repair genes, Lig3, Neil2, and Top3a, were also downregulated in the UVA-based mouse model of FECD. Our findings identify impaired DNA repair pathways that may play an important role in DNA damage due to oxidative stress as well as genetic predisposition noted in FECD.

Late-Onset Traumatic Corneal Conjunctival Epithelial Disorders due to Granular Formation After Cosmetic Suture Blepharoplasty.

The purpose of this study was to report conjunctival granular formation as one of the causative factors of a traumatic corneal conjunctival epithelial disorder after plastic suture blepharoplasty. Clinical charts of 7 patients who had visited Ohshima Eye Hospital with a symptomatic corneal epithelial disorder and history of suture blepharoplasty were reviewed. Clinical evidence of conjunctival granular formations was observed in all patients at the tarsal conjunctiva facing to corneal conjunctival traumatic epithelial disorders. The desired outcome was to alleviate the disorder. The assessment included tabulating results after the placement of a soft contact lens bandage and subsequent partial tarsal plate resection of the granular formation. Seven women (mean age 45.0±10.9 years) enrolled in this study had previously undergone suture blepharoplasty (mean 18.3±6.9 years before). Soft contact lens bandages relieved all of the patients' complaints immediately. After resecting the granular formation, the traumatic corneal conjunctival epithelial disorder disappeared, and no recurrence was observed after surgery. The conjunctival granular formation within the tarsal conjunctiva after suture blepharoplasty caused the late-onset traumatic corneal conjunctival epithelial disorder. A complete cure was obtained after resection of the granular formation at the tarsal conjunctiva. To the best of our knowledge, this is the first report to identify the removal of granular formations in 7 patients with late-onset traumatic corneal conjunctival disorders many years after blepharoplasty. The resection of these lesions is a promising procedure to treat late-onset ocular epithelial disorder after suture blepharoplasty.

Late-Onset Obsessive-Compulsive Disorder With Religious Obsessions

Late-Onset Obsessive-Compulsive Disorder With Religious Obsessions

A mutation in the ZNF687 gene that is responsible for the severe form of Paget’s disease of bone causes severely altered bone remodeling and promotes hepatocellular carcinoma onset in a knock-in mouse model

Paget’s disease (PDB) is a late-onset bone remodeling disorder with a broad spectrum of symptoms and complications. One of the most aggressive forms is caused by the P937R mutation in the ZNF687 gene. Although the genetic involvement of ZNF687 in PDB has been extensively studied, the molecular mechanisms underlying this association remain unclear. Here, we describe the first Zfp687 knock-in mouse model and demonstrate that the mutation recapitulates the PDB phenotype, resulting in severely altered bone remodeling. Through microcomputed tomography analysis, we observed that 8-month-old mutant mice showed a mainly osteolytic phase, with a significant decrease in the trabecular bone volume affecting the femurs and the vertebrae. Conversely, osteoblast activity was deregulated, producing disorganized bone. Notably, this phenotype became pervasive in 16-month-old mice, where osteoblast function overtook bone resorption, as highlighted by the presence of woven bone in histological analyses, consistent with the PDB phenotype. Furthermore, we detected osteophytes and intervertebral disc degeneration, outlining for the first time the link between osteoarthritis and PDB in a PDB mouse model. RNA sequencing of wild-type and Zfp687 knockout RAW264.7 cells identified a set of genes involved in osteoclastogenesis potentially regulated by Zfp687, e.g., Tspan7, Cpe, Vegfc, and Ggt1, confirming its role in this process. Strikingly, in this mouse model, the mutation was also associated with a high penetrance of hepatocellular carcinomas. Thus, this study established an essential role of Zfp687 in the regulation of bone remodeling, offering the potential to therapeutically treat PDB, and underlines the oncogenic potential of ZNF687.

Modeling mitochondrial DNA diseases: from base editing to pluripotent stem-cell-derived organoids.

Mitochondrial DNA (mtDNA) diseases are multi-systemic disorders caused by mutations affecting a fraction or the entirety of mtDNA copies. Currently, there are no approved therapies for the majority of mtDNA diseases. Challenges associated with engineering mtDNA have in fact hindered the study of mtDNA defects. Despite these difficulties, it has been possible to develop valuable cellular and animal models of mtDNA diseases. Here, we describe recent advances in base editing of mtDNA and the generation of three-dimensional organoids from patient-derived human-induced pluripotent stem cells (iPSCs). Together with already available modeling tools, the combination of these novel technologies could allow determining the impact of specific mtDNA mutations in distinct human cell types and might help uncover how mtDNA mutation load segregates during tissue organization. iPSC-derived organoids could also represent a platform for the identification of treatment strategies and for probing the in vitro effectiveness of mtDNA gene therapies. These studies have the potential to increase our mechanistic understanding of mtDNA diseases and may open the way to highly needed and personalized therapeutic interventions.

Overview of late-onset psychoses.

Several etiologies can underlie the development of late-onset psychosis, defined by first psychotic episode after age 40 years. Late-onset psychosis is distressing to patients and caregivers, often difficult to diagnose and treat effectively, and associated with increased morbidity and mortality. The literature was reviewed with searches in Pubmed, MEDLINE, and the Cochrane library. Search terms included "psychosis," "delusions," hallucinations," "late onset," "secondary psychoses," "schizophrenia," bipolar disorder," "psychotic depression," "delirium," "dementia," "Alzheimer's," "Lewy body," "Parkinson's, "vascular dementia," and "frontotemporal dementia." This overview covers the epidemiology, clinical features, neurobiology, and therapeutics of late-onset psychoses. Late-onset schizophrenia, delusional disorder, and psychotic depression have unique clinical characteristics. The presentation of late-onset psychosis requires investigation for underlying etiologies of "secondary" psychosis, which include neurodegenerative, metabolic, infectious, inflammatory, nutritional, endocrine, and medication toxicity. In delirium, psychosis is common but controlled evidence is lacking to support psychotropic medication use. Delusions and hallucinations are common in Alzheimer's disease, and hallucinations are common in Parkinson's disease and Lewy body dementia. Psychosis in dementia is associated with increased agitation and a poor prognosis. Although commonly used, no medications are currently approved for treating psychosis in dementia patients in the USA and nonpharmacological interventions need consideration. The plethora of possible causes of late-onset psychosis requires accurate diagnosis, estimation of prognosis, and cautious clinical management because older adults have greater susceptibility to the adverse effects of psychotropic medications, particularly antipsychotics. Research is warranted on developing and testing efficacious and safe treatments for late-onset psychotic disorders.

DIMENSIONAL DIAGNOSIS IN SCHIZOPHRENIA SPECTRUM DISORDERS: A CASE REPORT

IntroductionThe use of diagnostic categories, although useful, fails in capturing the psychopathological complexity of the individual case. As for schizophrenia spectrum disorders, positive symptoms are not always included in the presentation, so further dimensions should be considered for a correct diagnosis.ObjectivesTo describe the importance of dimensional diagnosis in schizophrenia spectrum disorder based on a clinical experienceMethodsWe report the case of a late-onset schizophrenia spectrum disorder with an affective presentationResultsI. is a 44-year-old woman who accessed the Community Mental Health Center due to subjective memory complains. After clinical evaluation, depressive symptoms and circadian rhythm disturbances emerged. The patient also reported dissociative experiences, which emerged after her brother’s death. She underwent a neurological visit that excluded the possible early manifestation of a neurodegenerative disorder. Quetiapine was at first prescribed, due to the possible action on both insomnia and mood symptoms, with insufficient response. After a few visits, a deeper mental state examination revealed the presence of delusions. The patient also reported having experienced hallucinations. Psychotic symptoms appeared to be persistent and pervasive. We changed the antipsychotic to full-dose olanzapine, with good response. After a six-month observation, the patient was diagnosed with schizophrenia.ConclusionsThe diagnosis of late-onset schizophrenia should take into account clinical history, drugs response, and the evaluation of different psychopathological dimensionsDisclosure of InterestNone Declared

Spectrum of congenital and inherited ocular disorders seen in a genetic clinic: Experience of a developing ocular genetic service.

Hereditary causes are an important etiological category of childhood blindness. This study reports the real-world experience of a developing ocular genetic service. The study was carried out from Jan 2020 to Dec 2021 jointly by the Pediatric Genetic Clinic and the Department of Ophthalmology of a tertiary care hospital in North-West India. Children presenting to the genetic clinic with congenital or late-onset ocular disorder(s) and any individual (irrespective of age) suffering from an ophthalmic disorder and referred by an ophthalmologist for genetic counseling for himself/herself and/or his/her family member(s) were included. Genetic testing (exome sequencing/panel-based sequencing/chromosomal microarray) was outsourced to third-party laboratories with the cost of the test being borne by the patient. Exactly 8.6% of the registered patients in the genetic clinic had ocular disorders. Maximum number of patients belonged to the category of anterior segment dysgenesis, followed by microphthalmia anophthalmia coloboma spectrum, lens disorders, and inherited retinal disorders in decreasing numbers. The ratio of syndromic ocular to isolated ocular disorders seen was 1.8:1. Genetic testing was accepted by 55.5% of families. The genetic testing was clinically useful for ~35% of the tested cohort, with the opportunity for prenatal diagnosis being the most useful application of genetic testing. Syndromic ocular disorders are seen at a higher frequency compared to isolated ocular disorders in a genetic clinic. Opportunity for prenatal diagnosis is the most useful application of genetic testing in ocular disorders.

Diagnostic Instability Over Time in the Late-Onset Frontal Lobe Syndrome: When Can We Say it's FTD?

ObjectivesDistinguishing sporadic behavioral variant of frontotemporal dementia (bvFTD) from late-onset primary psychiatric disorders (PPD) remains challenging with the lack of robust biomarkers. An early bvFTD misdiagnosis in PPD cases and vice-versa is common. Little is known about diagnostic (in)stability over longer period of time. We investigated diagnostic instability in a neuropsychiatric cohort up to 8 years after baseline visit and identified which clinical hallmarks contribute to diagnostic instability. DesignDiagnoses of participants of the late-onset frontal lobe (LOF) study were collected from the baseline visit (T0) and the 2-year follow-up visit (T2). Clinical outcomes were retrieved 5–8 years after baseline visit (Tfinal). Endpoint diagnoses were categorized into bvFTD, PPD and other neurological disorders (OND). We calculated the total amount of participants that switched diagnosis between T0-T2 and T2-Tfinal. Clinical records of participants that switched diagnosis were assessed. ResultsOf the 137 patients that were included in the study, the final diagnoses at Tfinal were bvFTD 24.1% (n = 33), PPD 39.4% (n = 54), OND 33.6% (n = 46) and unknown 2.9% (n = 4). Between T0 and T2, a total of 29 (21.2%) patients switched diagnosis. Between T2 and Tfinal, 8 (5.8%) patients switched diagnosis. Prolonged follow-up identified few cases with diagnostic instability. Major contributors to diagnostic instability where a nonconverting diagnosis of possible bvFTD and a probable bvFTD diagnosis based on informant-based history and an abnormal FDG-PET scan whilst having a normal MRI. ConclusionConsidering these lessons, a FTD diagnosis remains stable enough to conclude that 2 years is sufficient to say if a patient with late-life behavioral disorder has FTD.

A late-onset neurological disorder: Is progression inevitable? Expert Commentary

In this month's Movement Disorders Rounds, Dr. Shoaib Dal and colleagues describe an interesting patient with corticobasal syndrome (CBS) thought secondary to discrete asymmetric focal ischemic lesions affecting the cortical and immediate subcortical regions of the hand area of the primary motor cortex [1]. The patient was an 88 year-old right-handed man with a history of coronary artery disease who presented with recurrent presyncopal events and a 2-year history of slowly progressive left-hand clumsiness, tremor, and gait disturbance.

Clinical characteristics of late-onset neuromyelitis optica spectrum disorder.

Anti-aquaporin-4 (AQP-4) immunoglobulin G (IgG) is a major autoimmune antibody that contributes to the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD). NMOSD often presents as disability, severe sensory impairment, and sleep disorders, which can cause anxiety and depression and further affect the quality of life. The age of onset is a key factor influencing the prognosis of NMOSD. However, this result was based on studies involving only anti-aquaporin-4 (AQP4) immunoglobulin G (IgG)-seropositive NMOSD patients or studies using the 2006 NMOSD diagnosis criteria. Therefore, further study of the age of onset of NMOSD is valuable. This study aimed to describe the clinical and magnetic resonance imaging (MRI) differences between early-onset neuromyelitis optica spectrum disorder (EO-NMOSD) and late-onset (LO)-NMOSD patients. Fifty patients were enrolled, their anti-AQP4-IgG titers were measured, and brain and spinal cord MRIs were obtained. Additionally, several questionnaires related to disease severity, anxiety, depression, cognition, sleep, pain, and fatigue were collected. Higher AQP4-IgG seropositivity, higher AQP4-IgG titer, frequency of thoracic myelitis, and white matter hyperintensities (WMH), as well as greater severity of disability, greater severity of sleep disorders, higher anxiety, poorer cognitive function, and higher clinical dementia rating (CDR)-community affairs scores were observed in late-onset (LO)-NMOSD patients than those in early-onset (EO)-NMOSD. AQP4-IgG titer positively correlated with age, annual relapse rate, Expanded Disability Status Scale (EDSS) sensory scores, Activity of Daily Living Scale (ADL) scores, and Pittsburgh Sleep Quality Index (PSQI) scores. The EDSS-sensory scores positively correlated with age, relapse time, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, PSQI, ADL, and CDR. WMH was positively correlated with age, EDSS-sensory scores, PSQI scores, and CDR scores and negatively correlated with the California Verbal Learning Test scores. LO-NMOSD patients have worse prognoses than those of EO-NMOSD patients. Higher AQP4-IgG titers, more WMHs, thoracic myelitis, and severe sensory symptoms are associated with cognition, depression, anxiety, and sleep disorders.

A curious case of confusion

A curious case of confusion

ТРУДНОКУРАБЕЛЬНЫЙ СЛУЧАЙ ШИЗОТИПИЧЕСКОГО РАССТРОЙСТВА: КЛИНИЧЕСКИЙ ПРИМЕР

A difficult-to-treat case of late-onset schizotypal disorder, accompanied by obsessive-compulsive symptoms, has been treated by specialists as a psychogenic pathology for many years. The characteristics of diagnosis, the dynamics of psychopathological symptoms, and treatment approaches with an assessment of their effectiveness are analyzed.

Association between Late Manifestations of Testicular Dysgenesis Syndrome and Anogenital Distance: A Systematic Review and Meta-analysis.

In 2001, Skakkebæk et al. proposed that certain male reproductive disorders might be grouped into a syndrome called testicular dysgenesis syndrome (TDS), as they all appear to be associated with disruption of the embryonic and foetal programming of gonadal development. TDS may be manifested in early life by the presence of genital malformations (hypospadias and cryptorchidism) and in adult life as disorders represented by low sperm counts and testicular cancer. Changes in androgen hormones during the foetal development, in addition to resulting in TDS, can also cause permanent changes in anopenile anogenital distance (AGDap) and anoscrotal anogenital distance (AGDas). The objective of this study was to determine whether there is a relationship between late manifestations of TDS and reduced anogenital/anoscrotal distance. The present study is a systematic review and meta-analysis. The research included papers from 2001 to 2020, comprising a total of 737 articles, and 13 articles were selected. Linear regression analysis was performed to evaluate the relationship between the two anogenital distance measures, which showed a significant positive association (P = 0.039). A meta-analysis was also performed and compared AGDap and AGDas between control and case groups, with cases defined as men with any late TDS manifestation. These data showed a significant reduction in AGDas in the affected population (P = 0.04), but no differences in the AGDap measure (P = 0.59). Our study confirmed a significant relationship between reduced AGDas and late manifestations of TDS, providing further support to the association between prenatal androgen deficiency and late-onset reproductive disorders.

Screening for the FMR1 premutation in Greek patients with late-onset movement disorders

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset, X-linked, neurodegenerative disorder that affects premutation carriers of the FMR1 gene. FXTAS is often misdiagnosed as spinocerebellar ataxia (SCA) or Parkinson's disease (PD). Herein, we sought to investigate the frequency, genotypic and phenotypic profile of FXTAS in two cohorts of Greek patients with late-onset movement disorders, one with cerebellar ataxia and the other with PD. In total, 90 index patients with late-onset cerebellar ataxia and 171 with PD were selected. None of the cases had male-to-male transmission. Genetic screening for the FMR1 premutation was performed using standard methodology. The FMR1 premutation was detected in two ataxia patients (2.2%) and two PD patients (1.2%). Additional clinical features in FXTAS patients from the ataxia cohort included neuropathy, mild parkinsonism, cognitive impairment and pyramidal signs. The FXTAS patients from the PD cohort had typical PD. We conclude that, in the Greek population, the FMR1 premutation is an important, albeit rare, cause of late-onset movement disorders. Routine premutation screening should be considered in SCA panel-negative late-onset ataxia cases. Directed premutation screening should be considered in all ataxia and PD cases with additional features suggestive of FXTAS. Our study highlights the importance of FMR1 genetic testing in the diagnosis of late-onset movement disorders.

Characteristics of people who have received treatment for late-onset problem drinking and alcohol use disorder: A systematic review and narrative synthesis.

Aims: The current review investigated the psychosocial characteristics of late-onset problem drinkers, an under-researched area of alcohol harm that accounts for one-third of older problem drinkers. Method: Following the PRISMA model, the protocol and search strategy included a scoping search and main search of nine databases. A total of 1,595 papers were identified; after screening, 26 papers were considered eligible and were included in the review. The review used an investigative framework comprising three categories: standardising age of onset; gender differences; and psychosocial and mental health characteristics. The review also investigated how meaning and purpose in life, and treatment have been reported in relation to this cohort. Findings/Conclusions: The combined onset ages of the reviews' 26 papers (mean age = 52.69 years) and the participants' self-reported age at onset (mean age = 56.79 years), suggest that late-onset alcohol use disorder (AUD)/problem drinking is likely to emerge at the age of 55 years and older. Moreover, there is a high prevalence of co-morbid mental health disorders among elderly, late-onset drinkers. Retirement was reported as the most prevalent psychosocial risk factor for late-onset problematic drinking; other late-life events included bereavement, loneliness and social isolation, and boredom. In the context of gender, women are at greater risk of developing late-onset problem drinking than men. Furthermore, late-onset problem drinkers, particularly women, are more treatment compliant than their early-onset counterparts, highlighting the case for bespoke treatments/interventions for late-onset problem drinkers. Finally, the role that meaning and purpose in life plays in late-onset problem drinking has been under-reported and requires further investigation.

Early-Onset Parkinson's Disease: Creating the Right Environment for a Genetic Disorder.

Parkinson's disease (PD) by its common understanding is a late-onset sporadic movement disorder. However, there is a need to recognize not only the fact that PD pathogenesis expands beyond (or perhaps to) the brain but also that many early-onset patients develop motor signs before the age of 50 years. Indeed, studies have shown that it is likely the protein aggregation observed in the brains of patients with PD precedes the motor symptoms by perhaps a decade. Studies on early-onset forms of PD have shown it to be a heterogeneous disease with multiple genetic and environmental factors determining risk of different forms of disease. Genetic and neuropathological evidence suggests that there are α-synuclein centric forms (e.g., SNCA genomic triplication), and forms that are driven by a breakdown in mitochondrial function and specifically in the process of mitophagy and clearance of damaged mitochondria (e.g., PARKIN and PINK1 recessive loss-of-function mutations). Aligning genetic forms with recognized environmental influences will help better define patients, aid prognosis, and hopefully lead to more accurately targeted clinical trial design. Work is now needed to understand the cross-talk between these two pathomechanisms and determine a sense of independence, it is noted that autopsies studies for both have shown the presence or absence of α-synuclein aggregation. The integration of genetic and environmental data is critical to understand the etiology of early-onset forms of PD and determine how the different pathomechanisms crosstalk.

Identification of key genes in late-onset major depressive disorder through a co-expression network module.

Late-onset major depressive disorder (LOD) increases the risk of disability and suicide in elderly patients. However, the complex pathological mechanism of LOD still remains unclear. We selected 10 LOD patients and 12 healthy control samples from the GSE76826 dataset for statistical analysis. Under the screening criteria, 811 differentially expressed genes (DEGs) were screened. We obtained a total of two most clinically significant modules through the weighted gene co-expression network analysis (WGCNA). Functional analysis of the genes in the most clinically significant modules was performed to explore the potential mechanism of LOD, followed by protein-protein interaction (PPI) analysis and hub gene identification in the core area of the PPI network. Furthermore, we identified immune infiltrating cells using the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm between healthy subjects and LOD patients with the GSE98793 dataset. Next, six hub genes (CD27, IL7R, CXCL1, CCR7, IGLL5, and CD79A) were obtained by intersecting hub genes with DEGs, followed by verifying the diagnostic accuracy with the receiver operating characteristic curve (ROC). In addition, we constructed the least absolute shrinkage and selection operator (LASSO) regression model for hub gene cross-validation. Finally, we found that CD27 and IGLL5 were good diagnostic indicators of LOD, and CD27 may be the key gene of immune function change in LOD. In conclusion, our research shows that the changes in the immune function may be an important mechanism in the development of LOD, which can provide some guidance for the related research of LOD in the future.