Objective: To explore the mediating effects of psychological flexibility and exercise self-efficacy between frailty and social isolation among elderly patients with type 2 diabetes mellitus (T2DM), so as to provide the basis for alleviating social isolation in this population. Methods: From July to November 2024, elderly patients with T2DM aged ≥65 years were selected by using the convenience sampling method from the endocrinology and geriatrics departments of a tertiary hospital in Shanxi Province. Demographic and clinical data were collected using structured questionnaires. Frailty was assessed using the FRAIL Scale, psychological flexibility was measured with the Acceptance and Action Questionnaire-II (AAQ-II), exercise self-efficacy was evaluated via the Chinese version of the Exercise Self-Efficacy Scale, and social isolation was quantified employing the General Alienation Scale. The mediating effects of psychological flexibility and exercise self-efficacy between frailty and social isolation were analyzed using the Process macro program. Results: A total of 300 elderly patients with T2DM were included, with a mean age of (71.16±4.88) years. There are 167 males (55.67%) and 133 females (44.33%). The mean scores for frailty, psychological flexibility, exercise self-efficacy, and social isolation were (2.82±1.59), (28.32±6.95), (5.69±1.20), and (39.27±9.24). Mediation analysis revealed that frailty positively affected social isolation (β=0.227, 95%CI: 0.132-0.323). It also indirectly positively influenced social isolation through psychological flexibility (β=0.165, 95%CI: 0.105-0.234) and exercise self-efficacy (β=0.150, 95%CI: 0.093-0.217), and the chained mediating effect of psychological flexibility and exercise self-efficacy (β=0.066, 95%CI: 0.038-0.100). Conclusion Frailty exacerbates social isolation by diminishing psychological flexibility and exercise self-efficacy among elderly patients with T2DM.

Objective:To investigate the epileptogenic networks of bilateral asymmetric tonic seizures (BATS) originating from the posterior insula using stereo-electroencephalography (SEEG).Methods:A retrospective analysis was performed. Among the epilepsy patients who underwent preoperative assessment and SEEG monitoring in the Epilepsy Department of Guangdong Sanjiu Brain Hospital from January 1, 2015 to July 1, 2024, 7 patients with insular epilepsy characterized by BATS originating from the posterior insula were selected based on anatomo-electro-clinical characteristics. The clinical characteristics, neuroimaging features, scalp EEG patterns, and SEEG recordings of the 7 patients were collected and analyzed. Via synchronously analyzing ictal semiology and electroanatomical propagation pathways shown by SEEG, the features of epileptogenic networks were elucidated. Results:Four patients had seizure onset from the dorsal-superior part of the left posterior insula, and 3 patients from the dorsal-superior part of the right posterior insula. The electroencephalographic characteristics of the seizure onset zones showed high consistency in these 7 patients: rhythmic spike or multiple spike discharges at the initial stage, and a low-amplitude rapid rhythm pattern subsequently. Totally, 3-10 seizures were recorded in each patient. Four patients experienced prodromal symptoms, including 3 patients with somatosensory symptoms (1 with chest and abdominal pain, 1 with contralateral facial numbness combined with throat constriction sensation, and 1 with contralateral limb numbness), and 1 patient with non-specific presentation (hugging family member before seizure). The seizure semiological evolution sequence was from prodrome to BATS, and then to secondary symptoms, with 3 patients exhibiting clustered spasms as secondary symptoms, and 4 patients showing eyelids and contralateral upper limb distal tonic-clonic manifestations as secondary symptoms. The epileptogenic networks followed a consistent pattern: the dorsal-superior part of the posterior insula leads to the middle-posterior part of the superior circular sulcus, to the ventral posterior insular and posterior circular sulcus, and then to the supplementary sensorimotor area (SSMA), and finally to the central sulcus, central region-vertex, and inferior parietal lobule. Only 2 patients had the anterior insular-involved epileptic brain networks, while the remaining 5 patients did not involve the anterior insular. During BATS, SEEG electrode contacts corresponding to the posterior insular, superior circular sulcus and SSMA exhibited low-amplitude rapid rhythm patterns.Conclusion:The seizures spread from the dorsal-superior part of the posterior insula to the middle-posterior part of the superior circular sulcus at the early stage of onset, and then connected with SSMA; these structures formed a epileptogenic brain network through abnormal synchronous discharge, which eventually led to BATS.

Objective:The actor-partner interdependence model was used to explore the subject-object effect of family care on disease acceptance in maintenance hemodialysis (MHD) patients and their primary caregivers, and to provide empirical research support for formulating intervention strategies to improve the quality of life of MHD patients and their primary caregivers at the dyadic coping perspective.Methods:This study was a cross-sectional study. A convenience sampling method was used to select 223 pairs of MHD patients and their primary caregivers who received treatment at three hospitals from December 2023 to May 2024, namely the Second Affiliated Hospital of Guizhou Medical University, Qiandongnan People′s Hospital and Qiandongnan Traditional Chinese Medicine Hospital. The General Information Questionnaire, Family APGAR Index (APGAR) and the Acceptance of Illness Scale (AIS) were used to conduct the survey. An actor-partner interdependence model of the impact of family care levels on disease acceptance was constructed.Results:There were 223 patients with MHD, 134 males and 89 females, aged (48.41 ± 14.41) years. Among the 223 primary caregivers of MHD patients, 83 were males and 140 were females, aged (49.44 ± 12.40) years. The scores of APGAR and AIS for MHD patients were (7.92 ± 1.94), (20.45 ± 4.66) points, and (8.16 ± 1.67), (21.86 ± 3.54) points for their primary caregivers. There were statistically significant differences in scores ( t = - 2.28, - 7.69, both P<0.05). The results of correlation analysis showed that there was a significant positive correlation between the degree of family care of MHD patients and the disease acceptance of MHD patients, the family care of primary caregivers, and the disease acceptance of primary caregivers ( r = 0.454, 0.625, 0.515, all P<0.05). There was a significant positive correlation between the disease acceptance of MHD patients and the family care of their primary caregivers, the disease acceptance of primary caregivers, and the family care of primary caregivers and the disease acceptance of primary caregivers ( r = 0.442, 0.813, 0.495, all P<0.05). In terms of the actor effect, the level of family care positively influenced the disease acceptance for both MHD patients and their primary caregivers ( β = 0.715, 0.603, both P<0.001), the actor effect was significant. In terms of partner effect, there was a positive correlation between the family care levels of MHD patients and their primary caregivers and the disease acceptance of the other party ( β = 0.628, 0.725, both P<0.001), the partner effect was significant. Conclusions:There is an interactive effect between the disease acceptance of maintenance hemodialysis patients and their primary caregivers and their levels of family care.

Objective:The actor-partner interdependence model was used to explore the subject-object effect of family care on disease acceptance in maintenance hemodialysis (MHD) patients and their primary caregivers, and to provide empirical research support for formulating intervention strategies to improve the quality of life of MHD patients and their primary caregivers at the dyadic coping perspective.Methods:This study was a cross-sectional study. A convenience sampling method was used to select 223 pairs of MHD patients and their primary caregivers who received treatment at three hospitals from December 2023 to May 2024, namely the Second Affiliated Hospital of Guizhou Medical University, Qiandongnan People′s Hospital and Qiandongnan Traditional Chinese Medicine Hospital. The General Information Questionnaire, Family APGAR Index (APGAR) and the Acceptance of Illness Scale (AIS) were used to conduct the survey. An actor-partner interdependence model of the impact of family care levels on disease acceptance was constructed.Results:There were 223 patients with MHD, 134 males and 89 females, aged (48.41 ± 14.41) years. Among the 223 primary caregivers of MHD patients, 83 were males and 140 were females, aged (49.44 ± 12.40) years. The scores of APGAR and AIS for MHD patients were (7.92 ± 1.94), (20.45 ± 4.66) points, and (8.16 ± 1.67), (21.86 ± 3.54) points for their primary caregivers. There were statistically significant differences in scores ( t = - 2.28, - 7.69, both P<0.05). The results of correlation analysis showed that there was a significant positive correlation between the degree of family care of MHD patients and the disease acceptance of MHD patients, the family care of primary caregivers, and the disease acceptance of primary caregivers ( r = 0.454, 0.625, 0.515, all P<0.05). There was a significant positive correlation between the disease acceptance of MHD patients and the family care of their primary caregivers, the disease acceptance of primary caregivers, and the family care of primary caregivers and the disease acceptance of primary caregivers ( r = 0.442, 0.813, 0.495, all P<0.05). In terms of the actor effect, the level of family care positively influenced the disease acceptance for both MHD patients and their primary caregivers ( β = 0.715, 0.603, both P<0.001), the actor effect was significant. In terms of partner effect, there was a positive correlation between the family care levels of MHD patients and their primary caregivers and the disease acceptance of the other party ( β = 0.628, 0.725, both P<0.001), the partner effect was significant. Conclusions:There is an interactive effect between the disease acceptance of maintenance hemodialysis patients and their primary caregivers and their levels of family care.

Objective:To investigate the epileptogenic networks of bilateral asymmetric tonic seizures (BATS) originating from the posterior insula using stereo-electroencephalography (SEEG).Methods:A retrospective analysis was performed. Among the epilepsy patients who underwent preoperative assessment and SEEG monitoring in the Epilepsy Department of Guangdong Sanjiu Brain Hospital from January 1, 2015 to July 1, 2024, 7 patients with insular epilepsy characterized by BATS originating from the posterior insula were selected based on anatomo-electro-clinical characteristics. The clinical characteristics, neuroimaging features, scalp EEG patterns, and SEEG recordings of the 7 patients were collected and analyzed. Via synchronously analyzing ictal semiology and electroanatomical propagation pathways shown by SEEG, the features of epileptogenic networks were elucidated. Results:Four patients had seizure onset from the dorsal-superior part of the left posterior insula, and 3 patients from the dorsal-superior part of the right posterior insula. The electroencephalographic characteristics of the seizure onset zones showed high consistency in these 7 patients: rhythmic spike or multiple spike discharges at the initial stage, and a low-amplitude rapid rhythm pattern subsequently. Totally, 3-10 seizures were recorded in each patient. Four patients experienced prodromal symptoms, including 3 patients with somatosensory symptoms (1 with chest and abdominal pain, 1 with contralateral facial numbness combined with throat constriction sensation, and 1 with contralateral limb numbness), and 1 patient with non-specific presentation (hugging family member before seizure). The seizure semiological evolution sequence was from prodrome to BATS, and then to secondary symptoms, with 3 patients exhibiting clustered spasms as secondary symptoms, and 4 patients showing eyelids and contralateral upper limb distal tonic-clonic manifestations as secondary symptoms. The epileptogenic networks followed a consistent pattern: the dorsal-superior part of the posterior insula leads to the middle-posterior part of the superior circular sulcus, to the ventral posterior insular and posterior circular sulcus, and then to the supplementary sensorimotor area (SSMA), and finally to the central sulcus, central region-vertex, and inferior parietal lobule. Only 2 patients had the anterior insular-involved epileptic brain networks, while the remaining 5 patients did not involve the anterior insular. During BATS, SEEG electrode contacts corresponding to the posterior insular, superior circular sulcus and SSMA exhibited low-amplitude rapid rhythm patterns.Conclusion:The seizures spread from the dorsal-superior part of the posterior insula to the middle-posterior part of the superior circular sulcus at the early stage of onset, and then connected with SSMA; these structures formed a epileptogenic brain network through abnormal synchronous discharge, which eventually led to BATS.

Objective:To establish a lumbosacral triangle (composed of L 5 transverse process, S 1 superior articular process, sacral ala and iliac crest) classification and to guide L 5S 1 endoscopic surgery. Methods:A total of 647 patients with low back pain who admitted to Tianjin Hospital from January 2016 to October 2018 were retrospectively analyzed, including 315 males and 332 females, aged 42.9±15.1 years (range, 19-74 years). The L 5 transverse process sacral distance (TSD), inter trans-verse process length (ITL), interlaminar width (ILW), interlaminar height (ILH), iliosacral angle (ISA), iliac crest height (IH), intervertebral space height (ISH), intervertebral foramen height (IFH), and intervertebral foramen width (IFW) were measured based on lumbar spine anterior-posterior and lateral radiographs. Spearman correlation analysis and hierarchical cluster analysis were used to establish the lumbosacral triangle classification. A total of 822 patients underwent endoscopic L 5S 1 surgery based on lumbosacral triangle classification guidance and verification in Tianjin Hospital from January 2020 to December 2022, including 421 males and 401 females, aged 45.1±16.7 years (range, 15-79 years). The visual analogue scale (VAS) and Oswestry disability index (ODI) were compared before and after surgery, and the Macnab criteria were used to assess surgical outcomes. Results:Spearman correlation analysis showed positive correlations between IH and ISA ( r=0.75, P<0.001), IFH and IFW ( r=0.60, P<0.001), TSD and IFH ( r=0.53, P<0.001), and TSD and IFW ( r=0.40, P<0.001). There was a negative correlation between TSD and IH ( r=-0.46, P<0.001), TSD and ISA ( r=-0.42, P<0.001), IFW and ISA ( r=-0.41, P<0.001), IFW and IH ( r=-0.50, P<0.001), IFH and IH ( r=-0.42, P<0.001). According to Spearman correlation analysis, hierarchical cluster analysis and receiver operating characteristic curve, lumbosacral angle was divided into three types: Type 1, L5 transverse process overlapped with sacral alar; Type 2, 07 mm. Based on lumbosacral triangle classification, different endoscopic techniques were used at L5S1 in 822 patients, including interlaminar approach single-axis endoscopy, trans-foraminal approach single-axis endoscopy, trans-foraminal fenestration approach mobile microendoscopy and unilateral biportal endoscopy, the VAS and ODI of all the patients decreased than those preoperative in immediate postoperative period, half a year postoperative period and the final follow up, and the difference was statistically significant ( P<0.05). At the last follow-up, the Macnab score was excellent in 278 cases, good in 475 cases, and fair in 69 cases, with an excellent and good rate of 91.6% (753/822). Conclusion:Lumbosacral triangle classification is simple and practical, and can effectively guide L5S1 endoscopic surgery.

Objective:To establish an artificial intelligence-based surgical selection system utilizing deep learning to assist in the decision-making process for lumbar endoscopic surgery.Methods:General data of 1,110 patients who underwent percutaneous transforaminal endoscopic discectomy, 804 patients who underwent percutaneous interlaminar endoscopic discectomy, 923 patients who underwent mobile microendoscopic discectomy and 623 patients who underwent unilateral biportal endoscopic in Tianjin Hospital from January 2018 to June 2023 were included in the study. Clinical outcomes were assessed using the visual analogue scale (VAS) for leg and back pain, the Oswestry disability index (ODI), and MacNab criteria both before surgery and 12 months postoperatively. Using a random number table method, patients were divided into a training dataset (2,768 cases) and a test dataset (692 cases) at a ratio of 4∶1. Patient clinical symptoms, physical signs, and multi-modal imaging data were input into a deep learning model. This model was structured into three main modules: intervertebral disc detection, surgical necessity identification, and surgical recommendation. The final surgical method was determined using a convolutional neural network incorporating U-Net for segmentation and ResNet for classification. The accuracy and recall rates of each module were evaluated using the test dataset.Results:Compared to preoperative values, all patients showed significant improvements at the 12-month postoperative follow-up. For patients who underwent percutaneous transforaminal endoscopic discectomy, percutaneous interlaminar endoscopic discectomy, mobile microendoscopic discectomy, and unilateral biportal endoscopic surgery, the VAS scores for leg pain decreased from 7.69±0.80, 7.82±0.88, 7.62±0.69, and 7.56±1.00 preoperatively to 1.44±1.09, 1.35±0.82, 1.51±1.08, and 1.43±0.91 postoperatively. Similarly, the VAS scores for back pain decreased from 5.73±0.83, 6.17±0.99, 6.11±0.88, and 6.46±0.95 to 0.93±0.75, 1.01±0.67, 1.40±0.72, and 1.27±0.70, respectively. Additionally, the ODI significantly decreased from 39.91%±4.50%, 40.05%±8.05%, 47.08%±9.50%, and 44.43%±4.71% preoperatively to 5.77%±2.22%, 6.05%±2.31%, 8.51%±2.16%, and 9.51%±3.70% postoperatively, with all differences being statistically significant ( P<0.05). The excellent rate according to the MacNab criteria was 93.12% (3,222/3,460). In the deep learning model, the multi-modal data of 2,768 patients were input in the training set for deep learning to form a surgical identification and operation recommendation system, and the preoperative data of 692 patients were input in the test set to compare with the final operation method. In the intervertebral disc location module, the accuracy of location and designation of the five lumbar intervertebral discs was 97.1%(672/692). In the module of intervertebral disc need for surgery, the accuracy was 94.8%(3,280/3,460) and the recall rate was 91.9%(636/692). As for patients, the accuracy rate was 91.9%(636/692). In the operation recommendation module, the accuracy rate of operation recommendation based on intervertebral disc was 89.5%(569/636), and the accuracy rate of surgical recommendation based on patient was 82.2%(569/692). Conclusion:In this study, an artificial intelligent surgical procedures selection system based on deep learning was established, which could effectively integrate relevant data and accurately guide the selection of lumbar endoscopic surgery.

Objective:To explore the epileptogenic network patterns in 14 patients with mesial temporal lobe epilepsy (mTLE) originating from the amygdala.Methods:A total of 14 patients with mTLE originating from the amygdala underwent preoperative evaluation in Department of Epilepsy, Guangdong Sanjiu Brain Hospital from January 1, 2019 to December 31, 2023 were selected. A retrospective analysis was performed on the clinical data of these patients. Epileptogenic network patterns were further explored based on stereo-electroencephalogram (SEEG) and positron emission tomography-computed tomography (PET-CT).Results:Craniocerebral MRI indicated 12 patients with unilateral amygdala hypertrophy, and 2 with increased T2-FLAIR signal in the amygdala but no obvious volume change. During interictal period, scalp EEG indicated discharges in one or both temporal regions and distinguished at the lesion side. During ictal period, scalp EEG indicated that the initial side is consistent with the lesion side. Three clinical phenotypes and epileptogenic network patterns were summarized: the first type ( n=5) had clinical manifestations as aura→automotor→autonomic symptoms, with epileptic seizure starting from amygdala→hippocampus→preinsula→temporal pole (by SEEG) and low metabolism in the medial structures of the temporal lobe (by PET-CT); the second type ( n=6) had clinical manifestations as aura→hypermotor/complex motor→autonomic symptoms, with epileptic seizure starting from amygdala→hippocampus→temporal pole→frontal orbital gyrus and anterior cingulate cortex→insula (by SEEG) and low metabolism in the medial structures of the temporal lobe, temporal pole, insula, frontal-orbital gyrus, and inner frontal lobe (by PET-CT); the third type ( n=3) had clinical manifestations as aura→bilateral symmetrical dystonia→autonomic symptoms (with or without oral-alimentary automotor), with epileptic seizure starting from amygdala→hippocampus and insula→temporal pole and adjacent temporal neocortex (by SEEG) and low metabolism in the mesial structures of the temporal lobe and the insula (by PET-CT). Conclusion:The different clinical phenotypes of patients with mTLE originating from the amygdala may have equivalent epileptogenic network patterns.

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Objective:To explore the clinical and genetic features of two Chinese pedigrees affected with Autosomal dominant intellectual developmental disorder 49 (MRD49).Methods:Two MRD49 pedigrees which were admitted to the Children′s Hospital Affiliated to Shandong University respectively on January 28, 2021 and November 10, 2022 were selected as the study subjects. Clinical data of the two pedigrees were collected and analyzed. Genomic DNA was extracted from peripheral blood samples of the probands and their family members. The probands were subjected to mutational analysis by high-throughput sequencing. Candidate variants were validated using real-time fluorescence quantitative PCR (q-PCR) or Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Shandong University (No. SDFE-IRB/T-2022002).Results:Proband 1 had presented with language delay, motor retardation and intellectual disability, and his maternal grandmother, mother, aunt and cousin all had various degrees of intellectual disability. Sequencing results showed that proband 1 had deletion of exons 3 ~ 7 of the TRIP12 gene. q-PCR verification showed that his mother, aunt, maternal grandmother and cousin had all harbored the same deletion. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP1). Proband 2, who had mainly presented with language delay, motor retardation and intellectual disability, and was found to harbor a heterozygous c.3010C>T (p.Arg1004*) variant of the TRIP12 gene, which was verified to be de novo in origin. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:This study had diagnosed two MRD49 families through high-throughput sequencing. Above findings have enriched the phenotypic and mutational spectrum of MRD49 in China, which has also facilitated genetic counseling for the two pedigrees.