Objective:To determine the prevalence of GJB2 gene c. 109G>A (p.V37I) variant among infants with congenital hearing loss and analyze the initial audiological characteristics of children harboring the variant, compare the audiometric difference among individuals with various genotypes, and explore genetic and audiological manifestations of the affected families. Methods:One hundred twenty six infants diagnosed with congenital hearing loss at the Neonate Screening Center of Ningbo City from June 2021 to December 2024 were selected as the study subjects. The neonates, in addition with members from 16 of their families, had undergone genetic screening for variants of 208 hotspot sites within 24 deafness-associated genes. For cases identified with monoallelic variants and concurrent hearing loss, the full GJB2 gene was sequenced. Meanwhile, a retrospective analysis was carried out on 23 children whom were confirmed to have hearing loss and the c. 109G>A variant by whole exome sequencing from March 2022 to December 2024. And 102 children who were excluded to have hearing loss and pathogenic variants by whole exome sequencing were selected as normal controls. Audiological features of individuals harboring the c. 109G>A variant were compared. This study has been approved by the Medical Ethics Committee of The Affiliated Women and Children′s Hospital of Ningbo University (Ethics No.: EC2023-009). Results:For the 126 infants with congenital hearing loss, prospective screening has identified 58 (46.03%) to harbor the c. 109G>A variant. These included 38 homozygotes and 16 compound heterozygotes. Retrospective review of the 23 c. 109G>A positive children has identified 15 as homozygotes and 8 as compound heterozygotes. Genetic testing of the 16 pedigrees has identified 7 homozygotes and 1 compound heterozygote. For the homozygotes combined ( n=53), 96.2% exhibited bilateral symmetric hearing loss, with 78.3% showing high-frequency sloping patterns, and 98.1% having a hearing threshold ranging from 20 to 65 dB. For the compound heterozygotes combined ( n=24), 95.8% showed symmetric loss, with 59.4% having high-frequency sloping, and 97.9% had a hearing threshold ranging from 20 to 65 dB. Both groups showed significantly elevated ABR/PTA thresholds compared with the normal controls ( P=0.000). The compound heterozygous group had higher ABR thresholds (43.3 ± 15.0 dB nHL) compared with the homozygous group (39.1±12.0 dB nHL, P=0.005). Conclusion:Infants harboring the GJB2 c. 109G>A variant primarily manifest as mild-to-moderate, symmetric, high-frequency sloping hearing loss. Nearly one-third of affected children have thresholds between 20 to 35 dB nHL, suggesting that ABR > 35 dB nHL alone may underestimate the hearing impairment in this population. Compared with homozygotes, compound heterozygotes with the the GJB2 c. 109G>A variant can confer a more severe hearing loss.

Alzheimer's disease(AD), a neurodegenerative disorder associated with aging, is the most prevalent form of dementia.As the aging population continues to expand, AD presents significant health and caregiving challenges for families and society, making it a pressing international public health concern.In recent years, numerous countries have implemented dementia prevention and treatment strategies that emphasize community-based comprehensive approaches.Currently, the community-based AD prevention and treatment model in China is still in the exploratory phase, with community efforts lacking organization.In alignment with China's action plan for advancing dementia prevention and treatment, and to achieve the strategic objective of "healthy aging, " this consensus is based on the principle of three-level prevention and is tailored to the characteristics of AD disease progression.It aims to develop a comprehensive prevention and treatment strategy for AD that is suitable for communities in China, providing technical guidance and support to establish a scientific basis for formulating community AD prevention and treatment models.

Meckel′s cartilage (MC) was first delineated in 1820 by the German anatomist Johann Friedrich Meckel the Younger through his examination of human embryos. During early development, MC functions as a supportive structure for the mandible and serves as a template for the subsequent formation of the jaw bones. Ultimately, MC transforms into either skeletal tissue, ligaments, or completely resorbs, integrating with the continuously developing osseous structures. This review elucidates the influence of MC development and degeneration on mandibular morphogenesis, delineating cellular processes and key factors that govern chondrogenic fate determination. The analysis reveals how the alterations of MC affect mandibular and craniofacial development. As a transient cartilaginous structure, investigation into MC may yield valuable insights for understanding oral and craniomaxillofacial pathologies.

Objective:To investigate the clinical and genetic characteristics of patients with amyotrophic lateral sclerosis (ALS) caused by FUS gene mutations. Methods:A retrospective analysis was conducted on 7 families diagnosed with FUS gene related ALS in the Department of Neurology of Henan Provincial People′s Hospital from January 2018 to June 2024. Clinical data and neuroelectrophysiological results of the probands and family members were collected. Next generation sequencing or whole exome sequencing was conducted on the probands. The detected variants of the FUS gene were confirmed by Sanger sequencing. Results:Among the 7 probands, 4 were with familial ALS and 3 with sporadic ALS, including 6 males and 1 female. The average age of onset was 24.6 years (ranging from 21 to 30 years). The onset site included bulbar muscles in 1 case, proximal upper limbs in 3 cases, proximal lower limbs in 2 cases, and both upper and lower limbs in 1 case. Four patients presented both upper and lower motor neurons involvement on examination, and 3 had only lower motor neuron syndrome. Muscle atrophy and fasciculation were observed in 6 patients respectively, and dyspnea in 3 patients. Bilateral muscle strength was asymmetric in 5 patients. Proximal muscle weakness was predominant in 6 of the 7 patients with upper limb weakness, and 3 of the 5 patients with lower limb weakness. Electromyography showed neurogenic damage in all 7 cases. Five heterozygous variants of the FUS gene were detected in 7 patients, including 2 patients with c.1574C>T(p.P525L), 2 with c.1552A>G(p.R518G), 1 with c.1561C>T(p.R521C), 1 with c.1441delC(p.R481Efs *48), and 1 with both c.1574C>T(p.P525L) and c.430_447del(p.G144_Y149del) variants. The variant c.1441delC(p.R481Efs *48) had not been previously reported. During follow-up, 6 patients died of respiratory failure 6-18 months after onset, with an average of 11.8 months. Conclusions:Patients with FUS gene related ALS have an early age of onset, rapid progression, short survival period, asymmetric limb weakness, and more severe involvement of proximal limbs. The c.1574C>T(p.P525L) is a hotspot mutation, and the novel variant c.1441delC(p.R481Efs *48) enriches the mutation spectrum of the FUS gene.

Organ transplantation is an effective treatment for end-stage organ failure, but postoperative infections and rejection reactions are key factors affecting the survival of the patients. Recently, the incidence of human parvovirus B19 (B19V) infection following transplantation has increased. B19V is a non-enveloped virus that primarily infects the upper respiratory tract and exhibits significant tropism for erythroid progenitor cells in the bone marrow, leading to the lysis of erythrocytes and hematological abnormalities. After B19V viremia, it may further infect other cells, triggering inflammatory responses and tissue damage. B19V infection may lead to chronic anemia in organ transplant patients, thereby affecting the success of the transplant and the survival of the patients. Therefore, it is essential to diagnose and monitor B19V infection post-transplantation. Due to the immunosuppressive therapy following transplantation, traditional serological detection methods, such as IgM and IgG antibody tests, are often unreliable. In contrast, molecular biological detection, especially real-time fluorescent quantitative PCR technology, provides more accurate results. However, the diversity of B19V genotypes may lead to the missed detection of some genotypes. Thus, it is necessary to use different detection techniques to improve the diagnostic accuracy of B19 virus infections. Additionally, there is a need to explore more precise diagnostic methods to enhance the early identification and management of B19V infection, further improving the survival and life quality of the patients.

Objective:To investigate the clinical and genetic characteristics of spinal muscular atrophy (SMA) patients with SMN1 gene compound heterozygous mutations. Methods:Three SMA-Ⅲ pedigrees treated in Henan Provincial People′s Hospital from October 2019 to July 2020 were selected. The clinical data of 3 SMA-Ⅲ probands were retrospectively analyzed. Multiplex ligation-dependent probe amplification (MLPA) technology was used to detect the copy number of the SMN gene in the probands and their parents. Polymerase chain reaction amplification combined with microfluidic capillary electrophoresis were used to detect point mutations in the SMN1 gene of the probands. Sanger sequencing was used to validate candidate variant sites. Results:The 3 probands are all male, aged 19, 17 and 12 years, respectively. The main clinical manifestations were symmetrical muscle weakness mainly in the proximal lower limbs, mild to moderate elevation of serum creatine kinase, and neurogenic injury as determined by electromyography or muscle pathology. The genetic testing results showed that all 3 probands had heterozygous deletion in exon 7 of the SMN1 gene, and carried heterozygous variations c.275G>A (p.Trp92 *), c.689C>T (p.Ser230Leu), and c.708dupT (p.Pro237Serfs *19), respectively. The exon deletion and point mutation were inherited separately from their parents. c. 275G>A (p.Trp92 *) and c.708dupT (p.Pro237Serfs *19) variations had not been reported before. Conclusions:The clinical manifestations of SMA-Ⅲ patients are symmetrical muscle weakness, mainly in the proximal extremities of both lower limbs, and electromyography or muscle biopsy suggesting neurogenic lesions. The compound heterozygous variation of point mutation and heterozygous deletion in the SMN1 gene can lead to SMA-Ⅲ. Suspected SMA patients with SMN1 gene heterozygous deletion should take point mutation testing.

Objective:To analyze the clinical manifestations and muscular magnetic resonance imaging (MRI) features of 12 families with facioscapulohumeral muscular dystrophy (FSHD).Methods:Retrospective analysis was conducted on 12 FSHD families diagnosed by genetic testing at the Department of Neurology of Henan Provincial People′s Hospital from January 2017 to June 2021. Clinical data and lower limb muscle MRI results of the probands and related members of the families were collected, and the degree of muscle fatty degeneration shown in the MRI was scored using the modified Mercuri score.Results:There were 21 patients in 12 families, with the age of onset ranged from 10 to 47 years (mean 19.5 years). The course of disease ranged from 1 to 47 years (mean 23.1 years). The onset sites included unilateral upper extremity in 8 cases, bilateral proximal upper extremities in 9 cases, bilateral proximal lower extremities in 2 cases, unilateral proximal lower extremity in 1 case, and simultaneous onset in all 4 limbs in 1 case. Sixteen patients had limb weakness and bilateral asymmetry, and 11/16 cases were more severe on the right side than the left side. Winged scapular and facial muscle weakness were observed in all patients. The creatine kinase range was 85-1 038 U/L (461 U/L on average) in 12/21 cases. There were 10/21 cases of myogenic lesion in electromyography. Myodystroph-like pathological changes were found in 11/21 cases. The fragment length of the 4q35 subtelomere polymorphism EcoRI/p13E-11 was less than 38 kb in 20/21 cases; 1 case was confirmed based on clinical symptoms and family history. Fat infiltration occurred in at least one muscle of lower limbs in 9/10 cases, in thigh muscle in 9/10 cases and in calf muscle in 6/10 cases. The average score of fat infiltration in thigh muscle group was higher than that in calf muscle group. The muscles with higher fat infiltration scores were the vastus intermedius, the long head of the biceps femoris, the vastus medialis, the vastus lateralis, the semitendinosus, the semimembranosus, the vastus lateralis in the thigh (with score ≥2.15), the tibialis anterior, and the medial head of the gastrocnemius in the calf (with score ≥1.11). Fat infiltration in the medial and posterior thigh muscles was more common than in the anterior thigh muscles. There was asymmetry of bilateral muscle fat in 9/10 cases. There were edematous changes in thigh muscles in 1 case and in calf muscles in 3 cases.Conclusions:The age of onset of FSHD patients is mostly ≤30 years. Bilateral asymmetric involvement is the characteristic manifestation of FSHD. The FSHD patients ' muscles most affected by the disease in the thigh are the quadriceps femoris, the long head of the biceps femoris, the vastus medialis, the vastus lateralis, the semitendinosus, the semimembranosus, and the vastus intermedius. In the calf, the muscles most affected are the anterior tibial muscle and the medial head of the gastrocnemius. The MRI pattern of muscle involvement of patients with FSHD is bilateral asymmetrical lesions, with the right side having more severe lesions. The fatization of thigh muscles is more significant than that of calf muscles, and the asymmetry of fatization between bilateral muscles is also present.