Objective To investigate the association of sleep disorders with the development and progression of nonalcoholic fatty liver disease(NAFLD).Methods A total of 1 868 participants from the health examination cohort and fatty liver cohort of Beijing Friendship Hospital from June 2022 to June 2023 were enrolled as subjects.Related data were collected from all subjects,including age,sex,education level,chronic medical history,and biochemical parameters,and all subjects completed Pittsburgh Sleep Quality Index(PSQI)scale independently.According to the diagnostic criteria,the subjects were divided into non-NAFLD group with 1 122 subjects and NAFLD group with 746 subjects,and according to the stage of progression,the patients in the NAFLD group were further divided into simple fatty liver group(SFL group with 624 subjects)and nonalcoholic steatohepatitis(NASH)group with 122 subjects.A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between three groups.The chi-square test was used for comparison of categorical data between the three groups.The binary Logistic regression analysis was used to investigate the association between sleep factors and NAFLD,and the multinomial Logistic regression analysis was used to investigate the association between sleep factors and the different stages of NAFLD;two multivariate models were constructed for adjustment of potential confounding factors,i.e.,an age-sex adjustment model and a multivariate adjustment model,and the multivariate adjustment model adjusted the factors of age,sex,education level,smoking,diabetes,hypertension,body mass index(BMI),triglyceride(TG),and high-density lipoprotein cholesterol(HDL-C).Results There were significant differences in age,sex,BMI,education level,smoking,diabetes,hypertension,alanine aminotransferase,TG,and HDL-C between the non-NAFLD,SFL,and NASH groups(all P<0.05).There were also significant differences between the three groups in the total score of PSQI scale and the proportion of subjects with a score of 0—3 points for the 7 sleep components(all P<0.05).The multivariate adjustment model showed no significant association between sleep disorders and SFL,while long sleep latency(odds ratio[OR]=4.04,95%confidence interval[CI]:2.33—7.03,P<0.001),short sleep duration(OR=3.53,95%CI:1.83—6.82,P<0.001),and severe sleep disorders(OR=2.96,95%CI:1.48—5.93,P=0.002)were closely associated with the risk of NASH.Conclusion Overall sleep condition and its components of sleep disorders are not significantly associated with the simple fatty liver;however,long sleep latency,short sleep duration,and severe sleep disorders can increase the risk of NASH,which should be taken seriously in clinical practice.

Purpose: This study explored the performance of prenatal ultrasonography in the differential diagnosis of cystic biliary atresia (CBA) and choledochal cyst (CC). Methods: Fetuses diagnosed with hepatic hilar cyst in the second trimester were included in this study. A series of prenatal ultrasound examinations were performed in the second and third trimesters. The diameter of the gallbladder (GB) and hepatic cyst were measured, as well as the wall thickness of the GB. The GB-cyst connection, visibility of the right hepatic artery (RHA), and other concomitant abnormalities were carefully evaluated. A neonatal transabdominal ultrasound examination was performed within 1 week after birth, and clinical data were followed up to 6 months after birth. Results: Between January 1, 2016 and January 31, 2020, 53 fetuses diagnosed with hepatic hilar cyst were recruited. Eight were excluded because they were lost to follow-up. Among the 45 cases included in this study, 10 were diagnosed with CBA and 35 with CC after birth. Statistically significant differences were found in GB width, wall thickness, change in GB width, change in cyst length, GB-cyst connection, and RHA visibility between the CBA and CC groups. GB width showed the best diagnostic performance with an area under the curve (AUC) of 0.899. The combination of GB width, GB wall thickness, and GB-cyst connection yielded a comparable AUC of 0.971. Conclusion The GB should be carefully evaluated in fetuses with hepatic hilar cyst. Prenatal ultrasound findings could provide suggestive parameters for the differential diagnosis of CBA from CC.

OBJECTIVE: To explore the genetic basis for a child featuring congenital insensitivity to pain (CIP). METHODS: Targeted capture and next generation sequencing (NGS) was carried out for the proband. Suspected pathogenic variants were confirmed by Sanger sequencing of the proband and his parents. RESULTS: The proband was found to harbor compound heterozygous variants of SCN9A gene, namely c.1598delA (p.N533Ifs*31) and c.295_296delCGinsAT (p.R99I), which were respectively inherited from his father and mother. Both variants were predicted to be pathogenic, and neither was reported previously. CONCLUSION The compound heterozygous variants of the SCN9A gene probably underlay the CIP in this child. Above finding has enabled genetic counseling for this family.
Channelopathies ; Child ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; NAV1.7 Voltage-Gated Sodium Channel/genetics* ; Pain Insensitivity, Congenital/genetics*

OBJECTIVE: To explore the genetic basis of a Chinese pedigree affected with progressive non-syndromic sensorineural hearing loss. METHODS: High-throughput DNA sequencing was carried out to analyze 415 genes associated with hereditary deafness in the proband. Sanger sequencing was carried out to verify the suspected variants among her family members. RESULTS: The proband was found to carry a heterozygous c.842T>A (p.Ile281Asn) variant of the POU4F3 gene. The same variant was found among all other patients from the pedigree including the proband's mother, brother, aunt and maternal grandfather, but not among those with normal hearing. Based on the standards and guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, the c.842T>A(p.Ile281Asn) variant of the POU4F3 gene was predicted as likely pathogenic (PM2+PM5+PP1+PP3+PP4). CONCLUSION A Chinese pedigree affected by a rare type autosomal dominant deafness-15 (DFNA15) due to a novel c.842T>A (p.Ile281Asn) variant of the POU4F3 gene was identified. The result has facilitated genetic counseling and risk assessment for the pedigree.
China ; Deafness/genetics* ; Female ; Genetic Testing ; Hearing Loss, Sensorineural/genetics* ; Humans ; Male ; Mutation ; Pedigree

OBJECTIVE: To explore the genetic basis for a pedigree affected with congenital sensorineural deafness. METHODS: High-throughput sequencing was carried out to analyze the coding regions of 415 genes associated with hereditary deafness in the proband. Suspected variants were verified by PCR amplification and Sanger sequencing of her parents and sister. RESULTS: The proband was found to have carried a heterozygous c.5131G>A (p.Val1711Ile) variant of the CDH23 gene and a heterozygous c.2884C>T(p.Arg962Cys) variant of the PCDH15 gene, which were respectively inherited from her mother and father. Her sister (with normal hearing) was also heterozygous for the c.5131G>A (p.Val1711Ile) variant of the CDH23 gene but not the c.2884C>T (p.Arg962Cys) variant of the PCDH15 gene. Based on the guidelines of the American College of Medical Genetics and Genomics, both variants were predicted to be likely pathogenic (PS1+PM2+PP3+PP4). CONCLUSION The c.5131G>A (p.Val1711Ile) variant of the CDH23 gene and c.2884C>T (p.Arg962Cys) variant of the PCDH15 gene probably underlay the pathogenesis of Usher syndrome type 1D/F in this pedigree.
Female ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Pedigree ; Usher Syndromes/genetics*

Objective : To investigate the pathogenic factors and clinical manifestations of contact stomatitis, and to provide references for its clinical diagnosis and prevention. Methods: The data of 55 subjects with contact stomatitis were analyzed retrospectively, including age, gender, pathogenic factors, type of lesions and site of occurrence. Results: Among the 55 patients, contact stomatitis occurred at all ages, 19 were male, 36 were female, and the ratio of males to females was 1∶1.89. Among 55 patients, 78.18% (43/55) were caused by oral mucosal contact with dental materials: amalgam fillings accounted for 52.73% (29/55), metal crowns accounted for 9.09% (5/55), removable denture plastic bases accounted for 9.09% (5/55), resin fillings accounted for 5.45% (3/55), and alginate impression materials accounted for 1.82% (1/55); 21.82% (12/55) were caused by oral mucosal contact with food and daily necessities. The clinical manifestations of contact stomatitis include lichenoid reaction, erythema and erosion. The most common site of contact stomatitis was the cheek, followed by the tongue, and the lips, and the gingival and palatal areas were relatively rare. In the buccal mucosa, the incidence of lichenoid reaction was 55% (22/40), which was higher than that of erosion (20%) and erythema (25%), and the difference was statistically significant (P < 0.05). For tongue, lip, gingiva and palate, there was no significant difference in the incidence of the three lesion types（P > 0.05）. Conclusion Contact stomatitis occurred at all ages, and there are more female patients than males with contact stomatitis. Dental materials, especially metal and acrylic materials (such as the plastic base of removable dentures, resin fillings, adhesives, and self-setting plastics), are the main pathogenic factors. In buccal mucosa, the incidence of lichenoid reaction is higher.

OBJECTIVE: To detect variants of EXT1 and EXT2 genes among five pedigrees affected with multiple osteochondromas and provide prenatal diagnosis for the families based on the results. METHODS: The EXT1 and EXT2 genes of the probands were analyzed by targeted next generation sequencing (NGS). Suspected pathological variants were validated by Sanger sequencing in the probands, their family members and 200 unrelated healthy controls. Multiple ligation-dependent probe amplification (MLPA) was used to confirm the presence of gross deletions. Prenatal diagnosis was provided for 2 couples carrying pathogenic or likely pathogenic variants. RESULTS: Five variants were detected in the pedigrees, which included EXT1 exon 2-3 deletion, c.1468dupC (p.Leu490ProfsX31), c.2084delC (p.Pro695LeufsX11), and EXT2 c.187delT (p.Phe63SerfsX29) and c.1362T>G (p.Tyr454X). Among these, EXT1 exon 2-3 deletion, c.2084delC (p.Pro695LeufsX11) and EXT2 c.187delT (p.Phe63SerfsX29) were unreported previously. The three novel variants were not found among unaffected members of the pedigree and the 200 healthy controls. Upon prenatal diagnosis, the two fetuses were found to carry the same variants of the the probands. CONCLUSION Pathological variants of the EXT1 and EXT2 genes probably underlie the multiple osteochondromas among the 5 pedigrees. Prenatal diagnosis based on the results can effectively reduce the birth of further offspring affected with the disease.

OBJECTIVE: To explore the clinical and genetic features of a patient with mental retardation. METHODS: G-Banding chromosomal karyotyping and high-throughput sequencing was carried out for the child. Suspected variant was validated in his family by Sanger sequencing and bioinformatic analysis. RESULTS: The patient was found to carry a de novo heterozygous c.4090G>T (p.Gly1364X) variant of the ASXL3 gene, which was known to predispose to Bainbridge-Ropers syndrome. CONCLUSION The nonsense c.4090G>T (p.Gly1364X) variant probably accounts for the disease in this patient.
Child ; Codon, Nonsense ; Developmental Disabilities ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Intellectual Disability ; genetics ; Phenotype ; Syndrome ; Transcription Factors ; genetics

OBJECTIVETo detect potential mutations of COL1A1 and COL1A2 genes in four Chinese pedigrees affected with osteogenesis imperfecta (OI) and provide prenatal diagnosis for a fetus at 18th gestational week.

METHODSAll coding regions and exon/intron boundaries of the COL1A1 and COL1A2 genes were analyzed with targeted next-generation sequencing (NGS). Suspected mutations were confirmed with Sanger sequencing in the probands, unaffected relatives and 200 unrelated healthy individuals. Prenatal diagnosis for a high-risk fetus was carried out through Sanger sequencing.

RESULTSThe probands of families 1 and 2 have respectively carried a c.760G>A (p.Gly254Arg) and a c.608G>T (p.Gly203Val) mutation of the COL1A1 gene. For family 3, the proband and his daughter have carried a novel c.299-1G>C splicing mutation of the COL1A1 gene. The same mutation was not found in the fetus of this family. For family 4, the proband has carried a novel c.1990G>C (p.Gly664Arg) mutation of the COL1A2 gene. The four mutations were not found in the unaffected relatives and 200 unrelated healthy individuals.

CONCLUSIONThe mutations of the COL1A1 and COL1A2 genes probably underlie the disease in the four families. NGS combined with Sanger sequencing can provide an effective and accurate method for their genetic and prenatal diagnosis.

Adult ; Child, Preschool ; Collagen Type I ; genetics ; DNA Mutational Analysis ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Infant, Newborn ; Male ; Mutation ; Osteogenesis Imperfecta ; genetics ; Prenatal Diagnosis

Objective To investigate the clinical features and the therapeutic effects in patients with vestibu-lar paroxysmia(VP) .Methods A total of 32 patients with VP were analyzed retrospectively through pure -tone au-diometry (PTA) ,auditory brainstem response(ABR) ,magnetic resonance imaging (MRI) ,and vestibular function . The effects were assessed after 3 months treatment of carbamazepine (CBZ) or oxcarbazepine (OXA) .Results The main clinical symptom of 32 patients was a brief spell of vertigo ,and 75% of patient's attacks were regularly precipi-tated by certain head positions or position changes .The most common accompanying symptom was unsteadiness of stance or gait (75 .00% ) .The PTA thresholds were elevated in 11 patients (34 .38% ) .MRI in all patients showed neurovascular cross -compression(NVCC) .Among 30 patients who performed ABR tests ,24 (80 .00% ) were ab-normal and 19 patients (63 .33% )were found that the interpeak latency (IPL) of wave I-III( IPL I-III) prolonged more than 2 .2 ms .The course of the patients with IPL I -III prolonged was relatively longer (P=0 .231) ,but there was no significantly difference .All patients received carbamazepine (CBZ) or oxcarbazepine (OXA) for one month .One case was lost to follow -up ,4 had no symptom improvement and 27 had a significant reduction in the attack frequency and intensity respectively after treatment of one month ,two months ,three months and 6 months of the drug withdrawal ,compared with the previous (P<0 .05) .The level of vertigo was significantly improved(P<0 .05) .Conclusion Episodic spells of vertigo are the main clinical symptom of VP ,regularly caused by certain head positions or position changes .The NVCC can be found by MRI in all patients .The IPL I -III in ABR was pro-longed in most patients ,some of them have hearing loss .CBZ and OXA are effective with VP and also significant in the experimental treatment of diagnosis .