identifying-immune-related-molecular-biomarkers-autism-spectrum

Identifying Immune-related Molecular Biomarkers in Autism Spectrum Disorder Using Data-independent Acquisition Proteomics and Machine Learning

This study presents a reproducible protocol for identifying serum protein biomarkers associated with autism spectrum disorder (ASD) using data-independent ...

Hunan Normal University

Changsha Maternal and Child Health Hospital, Affiliated to Hunan Normal University

Clustered regularly interspaced short palindromic repeats (CRISPR) systems are a set of versatile gene-editing toolkit that perform diverse revolutionary functions in various fields of application such as agricultural practices, food industry, biotechnology, biomedicine, and clinical research. Specially, as a novel antiviral method of choice, CRISPR/Cas9 system has been extensively and effectively exploited to fight against human infectious viruses. Infectious diseases including human immunodeficiency virus (HIV), hepatitis B virus (HBV), human papillomavirus (HPV), and other viruses are still global threats with persistent potential to probably cause pandemics. To facilitate virus removals, the CRISPR/Cas9 system has already been customized to confer new antiviral capabilities into host animals either by modifying host genome or by directly targeting viral inherent factors in the form of DNA. Although several limitations and difficulties still need to be conquered, this technology holds great promises in the treatment of human viral infectious diseases. In this review, we will first present a brief biological feature of CRISPR/Cas9 systems, which includes a description of CRISPR/Cas9 structure and composition; thereafter, we will focus on the investigations and applications that employ CRISPR/Cas9 system to combat several human infectious viruses and discuss challenges and future perspectives of using this new platform in the preclinical and clinical settings as an antiviral strategy.

The Use of CRISPR/Cas9 as a Tool to Study Human Infectious Viruses.

Bohring-Opitz syndrome is a severe congenital disorder associated with a de novo mutation in the additional sex combs-like 1 (ASXL1) gene, and it is characterized by symptoms that include developmental delay and musculoskeletal and neurological features.

Bohring-Opitz syndrome caused by a novel ASXL1 mutation (c.3762delT) in an IVF baby: A case report.

Proximal hypospadias defects represent the most challenging aspect of maintaining blood supply to the flap, which eventually leads to a high rate of complications. We modified a sealed Y-shaped penis foreskin vascular protection technique, which can repair the urethra in a single stage. The inner plate of the foreskin was cut along the coronal sulcus, and both sides of the urethral plate were cut as deep as Buck's fascia. The "Y"-shaped foreskin flaps on both sides of the mouth that are continuous with the urethral plate were sutured to form a new urethral skin tube. The urethral skin tube was turned to the ventral side, and the foreskin was reshaped and sutured. A total of 89 children had their urinary catheters removed 4 weeks after the operation. All children were evaluated at least once a year for 3 consecutive years. There were 11 patients with urine leakage that occurred after the operation. These children, diagnosed with urine leakage, underwent successful repair after the leakage occurred. There were no urethral strictures after the operation. The one-time success rate of this operation was 87.6% (78/89), and the incidence of urethral fistula was 12.6% (11/89). The results showed that sealed Y-shaped penis foreskin vascular protection surgery was safer and had a higher operation rate than the traditional hypospadias repair technique. Modifying Koyanagi repair by our improved Koyanagi hypospadias repair is an excellent technique with relatively low complication rates.

Neomodified Koyanagi technique for severe hypospadias with one-stage sealed Y-shaped penis foreskin vascular protection surgery.

X-linked intellectual disability type Nascimento (XLID) is a rare disease caused by variants in the ubiquitin-conjugating enzyme E2A gene (UBE2A). Patients with XLID have similar phenotypes, including speech impairments, severe intellectual disability, hearing loss, wide facies, synophrys, generalized hirsutism, and urogenital abnormalities. Till date, only two splice-site variants of the UBE2A gene have been observed in patients with X-linked ID type Nascimento. Here, we report the case of a Chinese boy with a syndrome clinically similar to XLID with speech impairment, severe intellectual disability, and moderate hearing loss. However, different characteristics were also present in the patient, including an inability to maintain his head in an upright posture. Both of the patient's palms have a single transverse palmar crease. Subsequent whole-exome sequencing revealed a novel splice site variant in UBE2A (c.241 + 1 G > A). Our study not only expands the variant spectrum and clinical characteristics of UBE2A deficiency syndrome but also provides clinical evidence for genetic diagnoses.

A novel UBE2A splice site variant causing intellectual disability type Nascimento.

KAT6A syndrome is an autosomal dominant genetic disorder associated with intellectual disability due to mutations in the lysine acetyltransferase 6A () gene. There are some differences in phenotype between  gene variants. This current case report describes a 1-month-old male infant that had a nonsense mutation in the  gene. Neither of his parents had the mutation. The proband had feeding difficulties and a physical examination revealed the following: moderate dysphagia, hypoplastic laryngeal cartilage, poor audio-visual response, poor head-up ability, no active grasping awareness, microcephaly, high arched palate and he was significantly behind other children of the same age. Echocardiography showed that the foramen ovale was not closed. He was diagnosed with atrial septal defect (ASD) when 2 years old. The patient received ASD repair at 32 months of age. Head colour Doppler ultrasonography and brain magnetic resonance imaging showed cysts in the right ventricle and choroid plexus, which returned to normal at 2 years of age. This current case demonstrates that immediate surgery should be considered in newborns with KAT6A syndrome presenting with a heart malformation. A new KAT6A syndrome phenotype is described in this current case report, which requires early diagnosis and treatment.

The clinical spectrum of a nonsense mutation in : a case report.

Wiedemann-Steiner syndrome (WDSTS) is a rare autosomal dominant disorder caused by mutations in the KMT2A gene and is usually characterized by hairy elbows, short stature, developmental delay, intellectual disability and obvious facial dysmorphism.

A de novo mutation of ADAMTS8 in a patient with Wiedemann-Steiner syndrome.

THOC1 mutation causes Deafness, autosomal dominant 86 [OMIM: 620280]. However, it has not been reported whether deletion of the THOC1 gene causes deafness.

A patient with 18p11.32-p11.21 deletion have monaural deafness caused by an inadequate haplodose of THOC1: A case report.

Genetic factors significantly influence the concentration of metabolites in adults. Nevertheless, the genetic influence on neonatal metabolites remains uncertain. To bridge this gap, we employed genotype imputation techniques on large-scale low-pass genome data obtained from non-invasive prenatal testing. Subsequently, we conducted association studies on a total of 75 metabolic components in neonates. The study identified 19 previously reported associations and 11 novel associations between single-nucleotide polymorphisms and metabolic components. These associations were initially found in the discovery cohort (8,744 participants) and subsequently confirmed in a replication cohort (19,041 participants). The average heritability of metabolic components was estimated to be 76.2%, with a range of 69%-78.8%. These findings offer valuable insights into the genetic architecture of neonatal metabolism.

A genome-wide association study of neonatal metabolites.

This study reports a Chinese male patient with a novel MeCP2 p.Lys254*variant. Upon birth, the patient presented with typical symptoms, such as abnormal electroencephalogram, immature sleep rhythm, hypotonia, feeding difficulties, pulmonary fluid accumulation, horizontal fissures in the lungs, hypoventilation, and heart defects.

Proteomic analysis of serum from a MeCP2 patient reveals an arginine biosynthesis pathway affected by the p.Lys254* variant.

Cervical cancer is the second leading cause of death in women worldwide, second only to breast cancer. Around 80% of women have been infected with human papillomavirus (HPV) in their lifetime. Early screening and treatment are effective means of preventing cervical cancer, but due to economic reasons, many parts of the world do not have free screening programs to protect women's health.

New cheaper human papilloma virus mass screening strategy reduces cervical cancer incidence in Changsha city: A clinical trial.

Early diagnosis of autism is critical to its treatment, but so far, there is no clear molecular marker for early diagnosis in children.

Data independent acquisition proteomics and machine learning reveals that proteins associated with immunity are potential molecular markers for early diagnosis of autism.

Human papillomavirus (HPV) infection is a common sexually transmitted disease and a leading cause of cervical, other anogenital, and oropharyngeal cancers. Screening for precancerous lesions is an effective strategy for preventing HPV-related tumors. Although HPV vaccination has significantly reduced the incidence of cervical cancer, achieving universal coverage remains challenging because of cost barriers, particularly in economically disadvantaged regions. This review provides an update of HPV infection characteristics, screening methods, and strategies tailored to low-resource settings. We also discuss the global burden of HPV-related diseases, regional disparities in the implementation of screening, and future research directions. By examining the current challenges and opportunities, this review aims to inform policymakers and healthcare providers in designing effective, affordable, and scalable screening programs.

Article	Year
The Use of CRISPR/Cas9 as a Tool to Study Human Infectious Viruses. Frontiers in cellular and infection microbiology\| PubMed ID: 34513721	2021
Bohring-Opitz syndrome caused by a novel ASXL1 mutation (c.3762delT) in an IVF baby: A case report. Medicine\| PubMed ID: 35119035	2022
Neomodified Koyanagi technique for severe hypospadias with one-stage sealed Y-shaped penis foreskin vascular protection surgery. Clinical case reports\| PubMed ID: 35340636	2022
A novel UBE2A splice site variant causing intellectual disability type Nascimento. Clinical case reports\| PubMed ID: 35846913	2022
The clinical spectrum of a nonsense mutation in : a case report. The Journal of international medical research\| PubMed ID: 36573038	2022
A de novo mutation of ADAMTS8 in a patient with Wiedemann-Steiner syndrome. Molecular cytogenetics\| PubMed ID: 37649104	2023
A patient with 18p11.32-p11.21 deletion have monaural deafness caused by an inadequate haplodose of THOC1: A case report. Medicine\| PubMed ID: 39058882	2024
A genome-wide association study of neonatal metabolites. Cell genomics\| PubMed ID: 39389019	2024
Proteomic analysis of serum from a MeCP2 patient reveals an arginine biosynthesis pathway affected by the p.Lys254* variant. Clinical case reports\| PubMed ID: 39619318	2024
New cheaper human papilloma virus mass screening strategy reduces cervical cancer incidence in Changsha city: A clinical trial. World journal of clinical oncology\| PubMed ID: 39720646	2024
Data independent acquisition proteomics and machine learning reveals that proteins associated with immunity are potential molecular markers for early diagnosis of autism. Clinica chimica acta; international journal of clinical chemistry\| PubMed ID: 40185380	2025
Human papillomavirus infection and screening strategies. World journal of clinical oncology\| PubMed ID: 40503416	2025

Xiangwen Peng

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