Objective:To investigate the diagnostic value of preoperative fine-needle aspiration (FNA) of lymph nodes combined with washout thyroglobulin testing (FNA-Tg) for detecting lymph node metastasis in papillary thyroid carcinoma (PTC).Methods:A prospective study was conducted on 112 patients diagnosed with PTC at Wenzhou Central Hospital from December 2021 to December 2023, all of whom had suspicious lateral cervical lymph node metastasis identified through preoperative ultrasound. All patients underwent lymph node FNA and FNA-Tg. The suspicious lymph nodes were surgically excised. The diagnostic efficacy of FNA, FNA-Tg, and the combination of FNA and FNA-Tg for PTC with lymph node metastasis was compared.Results:A total of 112 patients were identified with 120 lymph nodes, among which 98 lymph nodes were confirmed to have metastasis by pathology. The results of the FNA cytology examination revealed 83 positive cases and 37 negative cases. The accuracy, sensitivity, and specificity for diagnosing lateral cervical lymph node metastasis were 80.83%, 80.61%, and 81.82%, respectively. In the FNA-Tg, there were 89 positive cases and 31 negative cases, with accuracy, sensitivity, and specificity for diagnosing lateral cervical lymph node metastasis at 89.17%, 88.78%, and 90.91%, respectively. When FNA and FNA-Tg were used in combination, there were 101 positive cases and 19 negative cases; the accuracy, sensitivity, and specificity for diagnosing lateral cervical lymph node metastasis were 94.17%, 97.96%, and 77.27%, respectively. The combined use of FNA and FNA-Tg demonstrated significantly higher accuracy in diagnosing metastatic lateral cervical lymph nodes in PTC compared to FNA and FNA-Tg alone ( χ2 = 50.64, P < 0.001; χ2 = 64.81, P < 0.001). Conclusions:The combined use of FNA and FNA-Tg demonstrates high accuracy in diagnosing lateral cervical lymph node metastasis in PTC.

Objective:To investigate the diagnostic value of preoperative fine-needle aspiration (FNA) of lymph nodes combined with washout thyroglobulin testing (FNA-Tg) for detecting lymph node metastasis in papillary thyroid carcinoma (PTC).Methods:A prospective study was conducted on 112 patients diagnosed with PTC at Wenzhou Central Hospital from December 2021 to December 2023, all of whom had suspicious lateral cervical lymph node metastasis identified through preoperative ultrasound. All patients underwent lymph node FNA and FNA-Tg. The suspicious lymph nodes were surgically excised. The diagnostic efficacy of FNA, FNA-Tg, and the combination of FNA and FNA-Tg for PTC with lymph node metastasis was compared.Results:A total of 112 patients were identified with 120 lymph nodes, among which 98 lymph nodes were confirmed to have metastasis by pathology. The results of the FNA cytology examination revealed 83 positive cases and 37 negative cases. The accuracy, sensitivity, and specificity for diagnosing lateral cervical lymph node metastasis were 80.83%, 80.61%, and 81.82%, respectively. In the FNA-Tg, there were 89 positive cases and 31 negative cases, with accuracy, sensitivity, and specificity for diagnosing lateral cervical lymph node metastasis at 89.17%, 88.78%, and 90.91%, respectively. When FNA and FNA-Tg were used in combination, there were 101 positive cases and 19 negative cases; the accuracy, sensitivity, and specificity for diagnosing lateral cervical lymph node metastasis were 94.17%, 97.96%, and 77.27%, respectively. The combined use of FNA and FNA-Tg demonstrated significantly higher accuracy in diagnosing metastatic lateral cervical lymph nodes in PTC compared to FNA and FNA-Tg alone ( χ2 = 50.64, P < 0.001; χ2 = 64.81, P < 0.001). Conclusions:The combined use of FNA and FNA-Tg demonstrates high accuracy in diagnosing lateral cervical lymph node metastasis in PTC.

Objective:To explore the clinical phenotype and genetic characteristics of two siblings with intellectual disability.Methods:Clinical data and peripheral blood samples were collected from the proband, his younger sister and parents whom had presented at Wenzhou Central Hospital in February 2024. Low-coverage massively parallel copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) were carried out for the family. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was performed on a fetus upon the couple′s subsequent pregnancy. The study was approved by the Medical Ethics Committee of Wenzhou Central Hospital(Ethic No.L2024-07-001).Results:The proband was a 12-year-old boy who had presented with mental retardation and language delay. His 10-year-old sister also manifested delayed mental and motor development. Whole exome sequencing revealed that the proband and his sister had respectively harbored a novel heterozygous c. 3549_3550del (p.Glu1183Aspfs*29) variant of the TRIP12 gene and a novel heterozygous c. 99del (p.Ser34Alafs*38) variant of the GRIN2B gene. Sanger sequencing confirmed that both variants had a de novo origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+ PS2_Supporting+ PM2_Supporting). Neither variant was found to be carried by the fetus upon prenatal diagnosis. Conclusion:Above variants probably underlay the mental disorders in the two siblings, and the concurrent occurrence of two novel pathogenic variants in a family has been extremely rare.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of two siblings with intellectual disability. METHODS: Clinical data and peripheral blood samples were collected from the proband, his younger sister and parents whom had presented at Wenzhou Central Hospital in February 2024. Low-coverage massively parallel copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) were carried out for the family. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was performed on a fetus upon the couple's subsequent pregnancy. The study was approved by the Medical Ethics Committee of Wenzhou Central Hospital (Ethic No. L2024-07-001). RESULTS: The proband was a 12-year-old boy who had presented with mental retardation and language delay. His 10-year-old sister also manifested delayed mental and motor development. Whole exome sequencing revealed that the proband and his sister had respectively harbored a novel heterozygous c.3549_3550del (p.Glu1183Aspfs*29) variant of the TRIP12 gene and a novel heterozygous c.99del (p.Ser34Alafs*38) variant of the GRIN2B gene. Sanger sequencing confirmed that both variants had a de novo origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PS2_Supporting+PM2_Supporting). Neither variant was found to be carried by the fetus upon prenatal diagnosis. CONCLUSION Above variants probably underlay the mental disorders in the two siblings, and the concurrent occurrence of two novel pathogenic variants in a family has been extremely rare.
Child ; Female ; Humans ; Male ; China ; DNA Copy Number Variations ; East Asian People/genetics* ; Exome Sequencing ; Genetic Testing ; Intellectual Disability/genetics* ; Mutation ; Pedigree ; Receptors, N-Methyl-D-Aspartate

Objective:To explore the clinical phenotype and genetic characteristics of two siblings with intellectual disability.Methods:Clinical data and peripheral blood samples were collected from the proband, his younger sister and parents whom had presented at Wenzhou Central Hospital in February 2024. Low-coverage massively parallel copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) were carried out for the family. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was performed on a fetus upon the couple′s subsequent pregnancy. The study was approved by the Medical Ethics Committee of Wenzhou Central Hospital(Ethic No.L2024-07-001).Results:The proband was a 12-year-old boy who had presented with mental retardation and language delay. His 10-year-old sister also manifested delayed mental and motor development. Whole exome sequencing revealed that the proband and his sister had respectively harbored a novel heterozygous c. 3549_3550del (p.Glu1183Aspfs*29) variant of the TRIP12 gene and a novel heterozygous c. 99del (p.Ser34Alafs*38) variant of the GRIN2B gene. Sanger sequencing confirmed that both variants had a de novo origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+ PS2_Supporting+ PM2_Supporting). Neither variant was found to be carried by the fetus upon prenatal diagnosis. Conclusion:Above variants probably underlay the mental disorders in the two siblings, and the concurrent occurrence of two novel pathogenic variants in a family has been extremely rare.

OBJECTIVE: To explore the genetic basis for two Chinese pedigrees affected with Coffin-Siris syndrome (CSS). METHODS: Whole exome sequencing (WES) was carried out for the probands. Candidate variants were verified by Sanger sequencing of the probands and their family members. RESULTS: The two probands were respectively found to harbor a heterozygous c.5467delG (p.Gly1823fs) variant and a heterozygous c.5584delA (p.Lys1862fs) variant of the ARID1B gene, which were both of de novo in origin and unreported previously. Based on the guidelines of American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION The c.5467delG (p.Gly1823fs) and c.5545delA (p.Lys1849fs) variants of the ARID1B genes probably underlay the CSS in the two probands. Above results have enabled genetic counselling and prenatal diagnosis for the pedigrees.
Abnormalities, Multiple ; China ; DNA-Binding Proteins/genetics* ; Face/abnormalities* ; Hand Deformities, Congenital ; Humans ; Intellectual Disability ; Micrognathism ; Neck/abnormalities* ; Pedigree ; Transcription Factors/genetics*

OBJECTIVETo establish individualized prenatal diagnosis program for families affected with Duchenne/Becker muscular dystrophy (DMD/BMD) and different clinical background using a variety of methods.

METHODSMultiplex ligation-dependent probe amplification (MLPA) was performed on 50 patients suspected for DMD/BMD. For single exon deletions of the DMD gene, PCR was used for validating the results. For those without any deletion or duplication, Sanger sequencing was used to screen for DMD gene mutations in the children and their mothers. Prenatal genetic testing was provided to female carriers using chorionic villus, amniocentesis or cord blood samples. To ensure the accuracy of diagnosis, all prenatal specimens were also subjected to linkage analysis.

RESULTSAmong the 50 patients with DMD/BMD, 23 harbored large deletions, 11 only had single exon deletions, 10 harbored duplications, and 5 had small scare mutations. No mutation was detected in one family. For 37 women undergoing prenatal diagnosis, 10 fetuses were identified as affected males, 6 were female carriers, while 21 were not found to carry any mutation. Testing of creatine kinase was consistent with the results of prenatal diagnosis. For a patient harboring exon 51 deletion, the same mutation was found in a fetus but not in their mother. The proband and fetus had inherited the same haplotype, which suggested that the mother probably has germline mosaicism for the mutation.

CONCLUSIONApplication of individualized methods for analyzing pregnant women with different clinical background can minimize the risk for giving birth to further children affected with DMD/BMD.

Adolescent ; Child ; Child, Preschool ; DNA Mutational Analysis ; Exons ; Female ; Humans ; Male ; Multiplex Polymerase Chain Reaction ; Muscular Dystrophy, Duchenne ; diagnosis ; genetics ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis

OBJECTIVETo analyze the clinical features and pathological mutations in 44 families affected with hearing loss from southern Zhejiang, and to provide genetic counseling and prenatal diagnosis for 6 of the families.

METHODSMicroarray was employed to detect c.35delG, c.176del16, c.235delC and c.299-300delAT mutations of the GJB2 gene among 228 patients. For those carrying a single heterozygous mutation, the whole coding region of the GJB2 gene was analyzed by Sanger sequencing. For prenatal diagnosis, maternal DNA contamination was excluded by application of STR analysis.

RESULTSThe microarray assay has detected 49 patients with GJB2 mutations, which included 24 homozygous c.235delC mutations, 5 compound heterozygous c.235delC/c.176del16 mutations, 2 compound heterozygous c.235delC/c.299-300delAT mutations. Respectively, 16, 1 and 1 patients have carried single heterozygous c.235delC, c.176del16, and c.299-300delAT mutation. For the 16 patients, 7, 1, 1, 2, and 3 were detected by Sanger sequencing with a second heterozygous mutation of c.109G>A (2 of which were in conjunction with heterozygous c.176del16 and c.299-300delAT mutations), c.230G>A, c.427C>T, c.508-511 dupAACG, 79G>A+341A>G, respectively. Prenatal diagnosis revealed a compound heterozygous mutation in a fetus, heterozygous mutations in 4 fetuses, and no mutation of the GJB2 gene in 1 fetus.

CONCLUSIONThe proportion of carriers for GJB2 gene mutations in patients with hearing loss from southern Zhejiang has reached 21.5%. The c.235delC, c.176del16, and compound c.299-300delAT and c.109G>A mutations can cause moderate to severe hearing loss. In most affected families, Heterozygous mutations may be identified by sequencing the whole coding region of the GJB2 gene. Genetic analysis and prenatal diagnosis can prevent birth of further affected children.

Connexins ; genetics ; Female ; Genetic Testing ; methods ; Hearing Loss ; genetics ; Heterozygote ; Humans ; Male ; Mutation ; genetics ; Phenotype

OBJECTIVETo carry out mutation analysis and prenatal diagnosis for 12 families affected with hearing loss and enlarged vestibular aqueduct from southern Zhejiang province.

METHODSClinical data and peripheral venous blood samples of 38 members from the 12 families were obtained. Mutations of 4 genes, namely SLC26A4, GJB2, c.538C to T and c.547G to A of GJB3, m.1555A to G and m.1494C to T of 12S rRNA, were detected by PCR and Sanger sequencing. Maternal contamination was excluded by application of STR detection during prenatal diagnosis.

RESULTSAmong the probands from the 12 families, 11 were found to be compound heterozygotes or homozygotes and 25 were heterozygotes. All of the families were detected with IVS7-2A to G mutations, and 4 had a second heterozygous mutation (c.2168A to G of the SLC26A4 gene). Four rare pathogenic mutations, namely IVS5-1G to A, c.946G to T, c.1607A to G and c.2167C to G, were detected in another four families. In addition, the partner of proband from pedigree 3 was identified with compound heterozygous mutations of c.235delC and c.299-300delAT, and proband of pedigree 5 has carried a mutation of c.109G to A in GJB2. For SLC26A4 gene, prenatal diagnostic testing has revealed heterozygous mutations in 6 fetuses and compound heterozygous mutations in 2 fetuses.

CONCLUSIONIVS7-2A to G and c.2168A to G of the SLC26A4 gene were the most common mutations in southern Zhejiang. Such mutations can be found in most families affected with hearing loss and enlarged vestibular aqueduct, which may facilitate genetic counseling and prenatal diagnosis for such families.

Adolescent ; Adult ; Base Sequence ; Child ; Child, Preschool ; DNA Mutational Analysis ; Female ; Fetal Diseases ; diagnosis ; genetics ; Hearing Loss ; diagnosis ; embryology ; genetics ; Hearing Loss, Sensorineural ; diagnosis ; embryology ; genetics ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Vestibular Aqueduct ; abnormalities ; embryology ; Young Adult

OBJECTIVETo analyze three cases with partial 21q trisomy, and correlate their genotypes with phenotypes.

METHODSG-banding chromosomal analysis and single nucleotide polymorphism (SNP array) were performed for the three cases and their parents.

RESULTSSNP array has detected partial 21q trisomy in three cases and one mother, with variable size and location of the duplications. Case 1 harbored a 12.35 Mb duplication at 21q22.11q22.3, which spanned the Down syndrome critical region. Case 2 harbored a 35.32 Mb duplication at 9p24.3p13.3 and a 14.42 Mb duplication at 21q11.2q21.3, with the former spanning the partial 9p trisomy syndrome critical region excluding the Down syndrome critical region, and was inherited from his mother. Case 3 harbored a 4.17 Mb tetraploidy at 21q11.2q21.1 in the form of mosaicism, which spared the Down syndrome critical region. His mother carried a 4.17 Mb triploidy at 21q11.2q21.1, which was also a mosaicism.

CONCLUSIONPartial 21q trisomy may occur in various forms and its clinical phenotypes are heterogeneous. Combined use of genetic techniques, particularly SNP array, is crucial for diagnosing partial 21q trisomy and delineating its genotype-phenotype correlation.

Child, Preschool ; Chromosome Banding ; Down Syndrome ; genetics ; Female ; Genotype ; Humans ; Infant ; Infant, Newborn ; Male ; Microarray Analysis ; methods ; Polymorphism, Single Nucleotide