Objective:To explore the genetic basis of a patient with suspected Oculocutaneous albinism (OCA).Methods:An OCA patient presented at the West China Second Hospital of Sichuan University and his mother were selected as the study subjects. Peripheral blood samples were collected for the extraction of genomic DNA, and whole exome sequencing (WES) was carried out. Candidate variants were verified through specific primer amplification, Sanger sequencing, and agarose gel electrophoresis. Bioinformatic analysis and pathogenicity rating were conducted on the candidate variants. This study has been approved by the Medical Ethics Committee of West China Second Hospital (No. 2024-228).Results:Genetic testing revealed that the patient had harbored variants in exon 1 of the TYR gene, including a c. 157G>T (p.G53C) missense variant and a c. 609dup (p.A204fs) frameshifting variant. Specific primer amplification and Sanger sequencing, combined with agarose gel electrophoresis, confirmed that these are compound heterozygous variants. Based on the guidelines from the ACMG, the c. 157G>T was rated as likely pathogenic, and c. 609dup was rated as pathogenic. Alphafold3 predicted that the variant proteins had significant structural changes. Conclusion:The patient was diagnosed with OCA due to compound heterozygous variants of the TYR gene. Discovery of the c. 609dup variant has enriched the mutational spectrum of OCA and provided a basis for genetic counseling and prenatal diagnosis for this patient.

OBJECTIVE: To explore the genetic basis of a patient with suspected Oculocutaneous albinism (OCA). METHODS: An OCA patient presented at the West China Second Hospital of Sichuan University and his mother were selected as the study subjects. Peripheral blood samples were collected for the extraction of, genomic DNA, and whole exome sequencing (WES) was carried out. Candidate variants were verified through specific primer amplification, Sanger sequencing, and agarose gel electrophoresis. Bioinformatic analysis and pathogenicity rating were conducted on the candidate variants. This study has been approved by the Medical Ethics Committee of West China Second Hospital (No. 2024-228). RESULTS: Genetic testing revealed that the patient had harbored variants in exon 1 of the TYR gene, including a c.157G>T (p.G53C) missense variant and a c.609dup (p.A204fs) frameshifting variant. Specific primer amplification and Sanger sequencing, combined with agarose gel electrophoresis, confirmed that these are compound heterozygous variants. Based on the guidelines from the ACMG, the c.157G>T was rated as likely pathogenic, and c.609dup was rated as pathogenic. Alphafold3 predicted that the variant proteins had significant structural changes. CONCLUSION The patient was diagnosed with OCA due to compound heterozygous variants of the TYR gene. Discovery of the c.609dup variant has enriched the mutational spectrum of OCA and provided a basis for genetic counseling and prenatal diagnosis for this patient.
Humans ; Albinism, Oculocutaneous/enzymology* ; Male ; Female ; Monophenol Monooxygenase/chemistry* ; Base Sequence ; Mutation, Missense

Objective:To explore the genetic basis of a patient with suspected Oculocutaneous albinism (OCA).Methods:An OCA patient presented at the West China Second Hospital of Sichuan University and his mother were selected as the study subjects. Peripheral blood samples were collected for the extraction of genomic DNA, and whole exome sequencing (WES) was carried out. Candidate variants were verified through specific primer amplification, Sanger sequencing, and agarose gel electrophoresis. Bioinformatic analysis and pathogenicity rating were conducted on the candidate variants. This study has been approved by the Medical Ethics Committee of West China Second Hospital (No. 2024-228).Results:Genetic testing revealed that the patient had harbored variants in exon 1 of the TYR gene, including a c. 157G>T (p.G53C) missense variant and a c. 609dup (p.A204fs) frameshifting variant. Specific primer amplification and Sanger sequencing, combined with agarose gel electrophoresis, confirmed that these are compound heterozygous variants. Based on the guidelines from the ACMG, the c. 157G>T was rated as likely pathogenic, and c. 609dup was rated as pathogenic. Alphafold3 predicted that the variant proteins had significant structural changes. Conclusion:The patient was diagnosed with OCA due to compound heterozygous variants of the TYR gene. Discovery of the c. 609dup variant has enriched the mutational spectrum of OCA and provided a basis for genetic counseling and prenatal diagnosis for this patient.

Objective:To investigate the prognosis of severe hyperbilirubinemia in full-term infants who met the exchange transfusion criteria and were treated by blood exchange transfusion and phototherapy.Methods:A total of 168 full-term infants with severe hyperbilirubinemia who met the criteria for exchange transfusion and were hospitalized in the Neonatology Department of seven tertiary hospitals in Hebei Province from June 2017 to December 2018 were retrospectively included. According to the treatment protocol, they were divided into two groups: exchange transfusion group (38 cases) and phototherapy group (130 cases). Two independent sample t-test and Chi-square test were used to compare the clinical manifestations and follow-up results between the two groups. Multivariate logistic regression was used to analyze the risk factors for poor prognosis. Results:Neonatal severe hyperbilirubinemia in the exchange transfusion and phototherapy group were both mainly caused by hemolytic disease [42.1%(16/38) and 29.2%(38/130)], sepsis [28.9%(11/38) and 11.5%(15/130)] and early-onset breastfeeding jaundice [15.8%(6/38) and 11.5%(15/130)]. Total serum bilirubin level on admission in the exchange transfusion group was significantly higher than that in the phototherapy group [(531.7±141.3) vs (440.0±67.4) μmol/L, t=3.870, P<0.001]. Moreover, the percentage of patients with mild, moderate and severe acute bilirubin encephalopathy in the exchange transfusion group were higher than those in the phototherapy group [15.8%(6/38) vs 3.8%(5/130), 7.9%(3/38) vs 0.8%(1/130), 13.2%(5/38) vs 0.0%(0/130); χ2=29.119, P<0.001]. Among the 168 patients, 135 were followed up to 18-36 months of age and 12 showed poor prognosis (developmental retardation or hearing impairment) with four in the exchange transfusion group (12.9%, 4/31) and eight in the phototherapy group (7.7%, 8/104). Multivariate logistic regression analysis showed that for full-term infants with severe hyperbilirubinemia who met the exchange transfusion criteria, phototherapy alone without blood exchange transfusion as well as severe ABE were risk factors for poor prognosis ( OR=14.407, 95% CI: 1.101-88.528, P=0.042; OR=16.561, 95% CI: 4.042-67.850, P<0.001). Conclusions:Full-term infants who have severe hyperbilirubinemia and meet the exchange transfusion criteria should be actively treated with blood exchange transfusion, especially for those with severe ABE, so as to improve the prognosis.

OBJECTIVE: Clinical examination and molecular genetic analysis were carried out for one case with special facial features with developmental retardation, hearing impairment and cleft lip and palate. METHODS: The intelligence test, hearing test, and MRI test were performed. At the same time, the blood were collected to detect the copy number variation of the whole genome with the chromosomal karyotype analysis and the chromosomal microarray analysis (CMA). And the whole exome sequencing (WES) was used to analyze the pathogenic variant. RESULTS: The children had mild mental retardation and the IQ was 61. There was moderate hearing loss in both ears(left ear 60 dB, right ear 65 dB). And bilateral horizontal hypoplasia of semicircular canal was found by cranial MRI test. No copy number abnormality was found by chromosome karyotype analysis and chromosome microarray analysis in peripheral blood. And whole exome sequencing suggested that there was heterozygous pathogenic variants in KMT2D gene (p.Leu545Argfs*385). CONCLUSION The patient has a peculiar face and multiple system defects, and was diagnosed as Niikawa-Kuroki syndrome type I by KMT2D gene variant. The whole exome sequencing is helpful for the diagnosis of complex genetic diseases.
Abnormalities, Multiple ; Child ; Cleft Lip ; Cleft Palate ; DNA Copy Number Variations ; Face/abnormalities* ; Hematologic Diseases ; Humans ; Vestibular Diseases

To screen the hearing loss and deafness-related genes in newborns,the screenings for hearing loss and the mutations of common deafness-related genes were performed among 8 187 infants born in Shaoxing Maternal and Child Health Care Hospital from August 2013 to November 2014.Twenty mutation spots in deafness-related genes GJB2,GJB3,12SrRNA and SLC26A4 were detected with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).Of 8 187 newborns,hearing loss was confirmed in 10 cases,and mutations in deafness-related genes were detected in 441 cases with a detection rate of 5.39％.Among 441 cases with positive gene mutations,there were 243 cases with GJB2 mutations (2.97％).147 cases with SCL26A4 mutations (1.80％),43 cases with GJB3 mutations (0.53％) and 15 cases with mutations of mitochondrial gene 12SrRNA (0.18％).The spot of highest detection frequency was GJB2 235delC (2.31％),followed by SCL26A4 IVS72A ＞ G (1.31％).The deafness gene detection rate for newborns who did not pass the hearing tests (8.16％,79/968) was higher than these who passed (5.01％,362/7 219;x2 =10.978,P ＜0.05).Five of 10 newborns with hearing loss were detected carrying deafness genes.The detection rate of the common deafness genes among the newborns is relatively high in this region.Screening for hearing loss and deafness gene may contribute to early diagnosis and intervention,and also to long-term precaution for those carrying heterozygosity deafness genes.

Objective To discuss the effect of grade repositioning designed by our team on preventing the development of pressure ulcers in ICU patients and its influence on nursing workload of repositioning. Methods Eligible patients admitted to ICU were randomly divided into control group (traditional repositioning,219 cases)and experimental group(grade repositioning,230 cases).The patients in control group was routinely repositioned every 2 hours;the patients in experimental group was classified as"A""B""C"three levels according to Braden Scores and catecholamine scores,and their repositioning frequency was 1 hour,2 hours and 4 hours respectively.Number of pressure ulcers and nursing workload of repositioning were observed and compared between the two groups. Results At last,the data analysis was included in 201 patients in control group and 220 patients in experimental group.There was no significant difference in the rate of pressure ulcer occurrence between the experimental group(0)and the control group[0.1%(2/201)](P>0.05).But the rate of skin redness occurrence was significant less in the experimental group than in the control group[1.36%(3/220)vs.11.44%(23/201), χ2=13.20,P<0.05]. The mean repositioning times for each patient in the experimental group was significantly less than the control group[(7.22±1.81)times/day vs.(11.38±1.23)times/day],and turn over time was(42.09±1.68)min and(66.35±1.83)min which was also significantly different(t=6.563, 5.210, P<0.05). Conclusion Grade repositioning could effectively prevent critically illed patients from the occurrence of pressure ulcers,while reducing the overall nursing workload of repositioning in an ICU.

OBJECTIVETo screen for common mutations of deafness-related genes in order to determine the carrier rate, types of mutation, and their relevance to hearing loss.

METHODSFor 4 deafness-related genes GJB2, GJB3, 12S rRNA and SLC26A4, 20 common mutations were screened among 2725 newborns from Shaoxing, Zhejiang by matrix-assisted laser desorption ionization-time of flight-mass spectrometry.

RESULTSAmong the 2725 newborns,149 (5.47%) were diagnosed with mutations, which included 84 (3.08%) with GJB2 mutations, 13 (0.48%) with GJB3 mutations, 49 (1.80%) with SLC26A4 mutations and 3 (0.11%) with 12S rRNA mutations. Fourteen mutational hotspots were identified. The most common mutations have included GJB2 c.235delC (65 cases), SLC26A4 IVS7-2A>G (34 cases), GJB2 c.299_300delAT (13 cases), GJB3 c.538C>T (7 cases), GJB2 c.176_191del16 (6 cases) and GJB3 c.547G>A (6 cases).

CONCLUSIONThe detecting rate for deafness-related gene mutations has been relatively high. To broaden the screening spectrum may improve such rate. Besides GJB2, 12S rRNA, SLC26A4, GJB3 also features a high mutation rate in the region.

Asian Continental Ancestry Group ; genetics ; China ; Connexin 26 ; Connexins ; genetics ; Deafness ; genetics ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Membrane Transport Proteins ; genetics ; Mutation ; Neonatal Screening ; RNA, Ribosomal ; genetics

Objective To study the quality of life(QOL) of patients with mild to moderate primary hypertension after treatment adjusted medication time by ambulatory blood pressure .Methods All 128 cases were divided into two groups randomly including chronos medication group and normal medication group .We tested ambulatory blood pressure ,QOL and influencing factors before medication and 6 months later .Results It′s observed the parameters of the ambulatory blood pressure improved significantly in all of the groups .There existed significant difference in nSBP ,nDBP ,nMAP ,SBP in dangerous night time ,and nocturnal blood pres‐sure decline rate between two groups (P<0 .05) .There existed very significant difference in DBP and MAP in dangerous night time (P<0 .01) .There were significant difference in the fields of MH (mental health) and RE (role limitation because of emotional health problem) (P<0 .05) ,and very significant difference in the fields of PF (physical functioning) ,RP (role limitation because of physical health) ,VT(vitality) (P<0 .01) .Multiple regression analysis indicate the influencing factors of the quality of life about patients with hypertension are age ,BMI index number ,medication time ,average family income ,medical insurance type ,culture de‐gree and job title .Age ,BMI index number and medication time depress QOL of patient with hypertension while average family in‐come ,better medical insurance type ,culture degree and job title improve it .Conclusion It′s possible to improved the parameters of the ambulatory blood pressure for patients with mild to moderate primary hypertension by chronos medication compared with nor‐mal medication more significantly .It′s useful to improve the QOL of patient with hypertension by improving average family income , medical insurance type and culture degree .

Objective To explore the effect of gestational hypertension on multiple organ system in neonates. Methods A total of 100 newborns whose mother had pregnancy complicating primary hypertension admitted to our hospital from December 2011 to December 2012 were selected and divided into preeclampsia group (n=53), gestational hypertension group (n=47) according to the blood pressure during pregnancy. Meanwhile, 100 newborns with healthy mother were selected as control group including 12 term infants and 88 premature infants. Data including birth weight, length and head circumference, Apgar score, the percentage of amniotic lfuid pollution, placental abruption and fetal distress, Neonatal Behavioral Neurological Assessment (NABA) score, serum level of creatine kinase, pulmonary arterial pressure, thyroid function, blood glucose, blood routine, cranial MRI parameters were collected and compared among three groups. Results In preeclampsia group, the gestational age, birth weight and head circumference, 1-min and 5-min Apgar scores were lowest while the ratio of low birth weight infants was highest among three groups, and the differences were signiifcant (P<0.05). In preeclampsia group, the rates of antenatal abnormalities (amniotic lfuid meconium III degree pollution, placental abruption and fetal distress) and complications (severe infection, myocardial damage, neonatal polycythemia, liver and kidney damage, hypoglycemia, hypothyroidism and respiratory failure) were highest among three groups, and the differences were signiifcant (P<0.01). In preeclampsia group, the red blood cell count, the levels of hemoglobin, hematocrit and thyroid stimulating hormone were signiifcantly higher than those in the other two groups ( P<0.05 ), and the white blood cell and platelet count was signiifcantly lower than that in the control group (P<0.05). The passive muscle tension scores in preeclampsia group were signiifcantly lower than those in the other two groups (P<0.05).The abnormity rate of cranial MRI in preeclampsia group was highest among three groups, and the difference was signiifcant (P<0.01). Conclusions Gestational hypertension may cause multisystem disorders in newborns, such as fetal intrauterine growth restriction, endocrine system disorders, heart dysfunction, increased blood viscosity, delayed neurodevelopment. The severity of gestational hypertension is associated with the adverse impact on the multiple systems in neonates.