OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with Branchio-Oto syndrome (BOS). METHODS: A pedigree with BOS which had presented at the Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University in May 2021 was selected as the study subject. Clinical data of the pedigree was collected. Peripheral blood samples of the proband and her parents were collected. Whole exome sequencing (WES) was carried out for the proband. Multiplex ligation-dependent probe amplification (MLPA) was used to verify the result of WES, short tandem repeat (STR) analysis was used to verify the relationship between the proband and her parents, and the pathogenicity of the candidate variant was analyzed. RESULTS: The proband, a 6-year-old girl, had manifested severe congenital deafness, along with inner ear malformation and bilateral branchial fistulae. WES revealed that she has harbored a heterozygous deletion of 2 466 kb at chromosome 8q13.3, which encompassed the EYA1 gene. MLPA confirmed that all of the 18 exons of the EYA1 gene were lost, and neither of her parents has carried the same deletion variant. STR analysis supported that both of her parents are biological parents. Based on the guidelines from the American College of Medical Genetics and Genomics, the deletion was classified as pathogenic (PVS1+PS2+PM2_Supporting+PP4). CONCLUSION The heterozygous deletion of EYA1 gene probably underlay the pathogenicity of BOS in the proband, which has provided a basis for the clinical diagnosis.
Humans ; Female ; Pregnancy ; Child ; Pedigree ; Family ; Parents ; Chromosomes, Human, Pair 3 ; Exons ; Nuclear Proteins/genetics* ; Protein Tyrosine Phosphatases ; Intracellular Signaling Peptides and Proteins/genetics*

OBJECTIVE: To investigate the clinical significance of AML patients with 11q23/MLL rearrangement, and to evaluate the effect of those mutations on the AML patients. METHODS: 53 cases involving translocations of chromosome 11q23 were identified by chromosome banding analysis. MLL rearrangements were detected by fluorescence in situ hybridization and/or multiplex nested PCR. The samples were screened for mutations in the candidate genes FLT3-ITD, FLT3-TKD, TET2, N-RAS, ASXLI, EZH2, DNMT3, C-Kit, NPM1, WT1, CEBPA by using genomic DNA-PCR and deep-sequencing. RESULTS: 21/53 MLL-rearranged AML cases showed at least one additional chromosomal aberrations. The most common additional aberration was +8. Gene mutations were observed in 23 cases (43.4%) and most cases showed singal mutation. N-RAS mutation was more frequent (8 cases, 15.1%), followed by WT1 mutation in 4 cases (7.5%), FLT3-ITD mutation in 3 cases, ASXL1 mutation in 2 cases, DNMT3A mutation in 2 cases, EZH2 mutation in 1 case, c-Kit17 mutation in 1 case, FLT3-TKD mutation in 1 case, and FLT3-ITD and TKD mutation coexistent in 1 case. No mutation was detected in CEBPA, NPM1, C-KIT8, TET2. Median OS for gene mutated patients was 8.5 months and 13 months for no mutated patients. Median OS for patients who received hematopoietic stem cell transplantation (HSCT) was 22.5 months and 7.5 months for patients who olny received chemotherapy. CONCLUSION A relatively high mutation frequency is observed in AML patients with 11q23/MLL rearrangements and most cases shows single mutation. The RAS signaling pathway alterations are most common. Gene mutation does not affect the OS of these patients, who show poor prognosis. A significantly higher Hb at initial diagnosis in FLT3 mutated patients is significantly higher than that in FLT3 wild-type cases. Patients who underwent HSCT show a better prognosis than those only received chemotherapy.
Chromosomes, Human, Pair 11 ; Hematopoietic Stem Cell Transplantation ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Myeloid, Acute ; Mutation ; Prognosis ; fms-Like Tyrosine Kinase 3

OBJECTIVE: To carry out prenatal diagnosis for a fetus with ultrasonographic abnormality. METHODS: Chromosomal karyotyping and array comparative genomic hybridization (array-CGH) analysis were applied for the diagnosis. Peripheral blood samples were also taken from the parents for chromosome karyotyping analysis. RESULTS: The fetal karyotype showed additional material of unknown-origin attached to Yq. Array CGH analysis confirmed that the material was derived from 3q22.1q29. The father was found to carry a balanced translocation 46, X, t(Y;3)(q12;q23) (which was diagnosed as 46,XY,Y≥18 elsewhere), whilst the mother was found to be normal. CONCLUSION 3q partial trisomy may present as malformation of multiple systems. Combination of chromosome karyotyping and array-CGH can provide reliable diagnosis for fetuses with abnormalities by ultrasonography.
Chromosomes, Human, Pair 3 ; genetics ; Comparative Genomic Hybridization ; Female ; Fetus ; Humans ; Karyotyping ; Male ; Pregnancy ; Prenatal Diagnosis ; Trisomy

Objective: To analyze the characteristics of myeloid neoplasms with t (3;21) (q26;q22) . Methods: Clinical data of patients with t (3; 21) (q26; q22) , diagnosed as hematologic malignancies in Peking University people's hospital from January 2011 to March 2018, were collected retrospectively. 19 patients in our hospital and forty-eight patients bearing t (3;21) (q26;q22) with detailed survival data reported in literature were summarized. Kaplan- Meier method was used for survival analysis. Results: Among 19 patients, including 15 males and 4 females with a median age of 36 years (22-68 years) , 4 cases was diagnosed as de novo acute myeloid leukemia (AML) , 4 as myelodysplastic syndromes (MDS) , 3 as MDS-AML and 8 as chronic myelogenous leukemia (CML) in myeloid blast transformation. All of the 19 patients were detected to have t (3;21) (q26;q22) by G-banding technique and 13 carried additional cytogenetic aberrations. 9 of the 19 patients were detected for positive AML1-MDS1 fusion genes. In the 9 patients with detailed follow-up data, 6 patients received chemotherapy and only 2 achieved complete remission (CR) while 4 with no response. During the follow-up period, 8 patients died and the median overall survival (OS) was 6 months (4.5 to 22 months) . Survival analysis of the present 9 patients together with the literature data showed that the prognosis was poor and the median OS was 7 months. In particular, AML/t-AML had the worst prognosis. Hematopoietic stem cell transplantation (HSCT) could significantly improve survival, the median OS in HSCT group and non-HSCT group were 20.9 and 4.7 months respectively (P<0.001) . Conclusions: t (3; 21) (q26; q22) is a rare recurrent chromosomal abnormality which is detected mainly in myeloid neoplasm and confer to poor clinical prognosis. HSCT should be recommended to improve the outcomes.
Adult ; Aged ; Chromosomes, Human, Pair 21 ; Chromosomes, Human, Pair 3 ; Female ; Humans ; Leukemia, Myeloid, Acute ; Male ; Middle Aged ; Myeloproliferative Disorders ; Retrospective Studies ; Translocation, Genetic ; Young Adult

OBJECTIVETo determine the nature of genomic copy number variations (CNVs) in two fetuses with congenital heart defects (CHD) and explore the correlation between 3q microdeletions and CHD.

METHODSGenomic DNA was extracted from fetal umbilical cord tissue, and chromosome copy number variations were detected by low coverage whole genome sequencing.

RESULTSBoth fetuses had microdeletions of the long arm of chromosome 3. Fetus 1 had ventricular septal defect, cleft lip and palate, and a 1.66 Mb deletion on 3q29. The deleted region encompassed all of the critical genes for 3q29 microdeletion syndrome. Fetus 2 had overriding aorta, ventricular septal defect, and a novel 240 kb deletion on 3q28.

CONCLUSION3q29 microdeletion may result in CHD in combination with cleft lip and palate. Genomic CNVs can be detected by low coverage whole genome sequencing.

Chromosome Deletion ; Chromosomes, Human, Pair 3 ; DNA Copy Number Variations ; Female ; Genetic Testing ; Heart Defects, Congenital ; genetics ; Humans ; Pregnancy ; Prenatal Diagnosis

OBJECTIVETodelineate the clinical and genetic features of a patient with myeloproliferative neoplasm (MPN) in association with PDGFRA and EVI1 genes rearrangements.

METHODSClinical data of the patient was collected. Conventional cytogenetics, fluorescence in situ hybridization (FISH) and nested PCR were carried out for the patient.

RESULTSThe patient has featured recurrent rash, joint pain, and intermittent fever. Laboratory tests showed hyperleukocytosis and marked eosinophilia. Physical examination revealed splenomegaly. His karyotype was 46,XY,t(3;5)(q26;q15)[6]/46,XY[10]. FISH assay showed that both PDGFRA and EVI1 genes were rearranged. Molecular studies of the mRNA suggested that there was a in-frame fusion between exon 12 of the PDGFRA gene and exon 9 of the FIP1L1 gene. Imatinib was initiated at a dosage of 200 mg, and after 10 months, the signal of the FIP1L1-PDGFRA fusion gene was undetectable in bone marrow sample. However, the expression of EVI1 mRNA was stable, with no significant difference found between the patient and 10 healthy controls.

CONCLUSIONMPN in association with PDGFRA and EVI1 genes rearrangements have unique clinical and genetic features. Genetic testing is helpful for early diagnosis. Imatinib may be effective for the treatment.

Antineoplastic Agents ; therapeutic use ; Base Sequence ; Chromosome Banding ; Chromosomes, Human, Pair 3 ; genetics ; Chromosomes, Human, Pair 5 ; genetics ; DNA-Binding Proteins ; genetics ; Gene Rearrangement ; Humans ; Imatinib Mesylate ; therapeutic use ; In Situ Hybridization, Fluorescence ; Karyotyping ; MDS1 and EVI1 Complex Locus Protein ; Male ; Myeloproliferative Disorders ; drug therapy ; genetics ; Proto-Oncogenes ; genetics ; Receptor, Platelet-Derived Growth Factor alpha ; genetics ; Transcription Factors ; genetics ; Translocation, Genetic ; Treatment Outcome ; Young Adult

OBJECTIVETo explore the genetic cause of a Chinese boy with unexplained mental retardation, and analyze the pattern of inheritance for his family.

METHODSRoutine karyotyping, chromosomal microarray analysis (CMA), and fluorescence in situ hybridization (FISH) were used to detect chromosome abnormalities in the patient and his families.

RESULTSChromosome analysis suggested that the proband and 7 affected individuals had an identical karyotype 46,XN,der(22)t(3;22)(q28;q13)pat, while his father and 5 other relatives carried a same karyotype of 46,XN,t(3;22)(q28;q13). His mother and other family members were normal. CMA analysis confirmed that the patient had a 9.0 Mb duplication at 3q28q29, in addition with a 1.7 Mb deletion at 22q13.3. Above results were confirmed by FISH.

CONCLUSIONThe abnormal phenotypes of the proband and his family members from five generations have conformed to those of 3q duplication and 22q13.3 deletion caused by unbalanced translocation involving chromosomes 3q and 22q. The presence of multiple patients in this family may be attributed to abnormal gametes produced by parental balanced translocations involving 3q and 22q.

Chromosome Deletion ; Chromosome Duplication ; Chromosomes, Human, Pair 22 ; genetics ; Chromosomes, Human, Pair 3 ; genetics ; Cytogenetic Analysis ; methods ; Family Health ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Intellectual Disability ; genetics ; Karyotyping ; Male ; Pedigree ; Translocation, Genetic

No abstract available.
Bone Marrow/pathology ; Chromosomes, Human, Pair 3 ; Chromosomes, Human, Pair 6 ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Lymphoma, Large B-Cell, Diffuse/*diagnosis/genetics ; Middle Aged ; Proto-Oncogene Proteins c-bcl-6/genetics ; Tomography, X-Ray Computed ; Translocation, Genetic

OBJECTIVETo investigate the genetic cause for a child with developmental delay and congenital heart disease through molecular cytogenetic analysis.

METHODSG-banded karyotyping and chromosomal microarray analysis (CMA) were performed for the patient and his parents.

RESULTSThe proband's karyotype was detected as ring chromosome 3, and a 3q26.3-25.3 deletion encompassing 45 genes has been found with CMA. Testing of both parents was normal.

CONCLUSIONClinical phenotype of the patient with ring chromosome 3 mainly depends on the involved genes. It is necessary to combine CMA and karyotyping for the diagnosis of ring chromosome, as CMA can provide more accurate information for variations of the genome.

Chromosomes, Human, Pair 3 ; genetics ; Cytogenetic Analysis ; methods ; Cytogenetics ; methods ; Developmental Disabilities ; genetics ; Female ; Heart Defects, Congenital ; genetics ; Humans ; Infant ; Karyotyping ; methods ; Ring Chromosomes ; Syndrome

OBJECTIVETo compare the results of fluorescence in situ hybridization (FISH) assay and conventional karyotyping analysis for the detection of chromosomal aneuploidies.

METHODSIn total 2607 amniotic fluid samples were subjected to an improved FISH technique. Meanwhile, karyotype analysis was also ordered for each sample.

RESULTSOf the 2607 samples, 62 abnormalities were identified by FISH, which included 62 cases of trisomy 21, 5 cases of 45,X, 12 cases of trisomy 18, 3 cases of trisomy 13, and 1 case of 47, XYY. Conventional karyotyping analysis has identified 63 cases of trisomy 21, 5 cases of 45,X, 12 cases of trisomy 18, 3 cases of trisomy 13, 1 case of 47, XYY, and 57 cases of balanced translocations. The success rate of FISH detection was 98.4% for trisomy 21, and 100% for 45,X, trisomy 18 and trisomy 13.

CONCLUSIONFor the detection of chromosomal aneuploidies, FISH assay is quick, simple, accurate and can reduce workload when aminocyte culture has failed. As an auxiliary method for amniocytic analysis, it can provide reference for the consultation of those with advanced age and high pregnancy risk.

Adult ; Amniocentesis ; methods ; Amniotic Fluid ; cytology ; metabolism ; Chromosomes, Human, Pair 18 ; genetics ; Chromosomes, Human, Pair 3 ; genetics ; Chromosomes, Human, Y ; genetics ; Down Syndrome ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Karyotype ; Karyotyping ; methods ; Middle Aged ; Pregnancy ; Reproducibility of Results ; Sensitivity and Specificity ; Sex Chromosome Aberrations ; Trisomy ; genetics ; Trisomy 18 Syndrome ; Turner Syndrome ; genetics ; Young Adult