Genetic diagnosis of Branchio-Oto syndrome pedigree due to a de novo heterozygous deletion of EYA1 gene / 中华医学遗传学杂志

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.

Clinical analysis of myeloid neoplasms with t (3;21) (q26;q22) / 中华血液学杂志

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.

Prenatal diagnosis of partial trisomy 3q in a fetus / 中华医学遗传学杂志

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.

Genetic analysis of two fetuses with congenital heart defects and 3q microdeletion / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Genomic DNA was extracted from fetal umbilical cord tissue, and chromosome copy number variations were detected by low coverage whole genome sequencing.</p><p><b>RESULTS</b>Both 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.</p><p><b>CONCLUSION</b>3q29 microdeletion may result in CHD in combination with cleft lip and palate. Genomic CNVs can be detected by low coverage whole genome sequencing.</p>

Clinical and molecular cytogenetic analysis of a family with mental retardation caused by an unbalanced translocation involving chromosomes 3 and 22 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genetic cause of a Chinese boy with unexplained mental retardation, and analyze the pattern of inheritance for his family.</p><p><b>METHODS</b>Routine karyotyping, chromosomal microarray analysis (CMA), and fluorescence in situ hybridization (FISH) were used to detect chromosome abnormalities in the patient and his families.</p><p><b>RESULTS</b>Chromosome 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.</p><p><b>CONCLUSION</b>The 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.</p>

Clinical and genetic features of a patient with myeloid neoplasm in association with PDGFRA and EVI1 gene rearrangements / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>Todelineate the clinical and genetic features of a patient with myeloproliferative neoplasm (MPN) in association with PDGFRA and EVI1 genes rearrangements.</p><p><b>METHODS</b>Clinical data of the patient was collected. Conventional cytogenetics, fluorescence in situ hybridization (FISH) and nested PCR were carried out for the patient.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>MPN 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.</p>

First Case of Diffuse Large B-Cell Lymphoma Subtype of Monomorphic Post-Transplant Lymphoproliferative Disorder With 3q27 Translocation

No abstract available.

Molecular cytogenetic analysis of a case with ring chromosome 3 syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the genetic cause for a child with developmental delay and congenital heart disease through molecular cytogenetic analysis.</p><p><b>METHODS</b>G-banded karyotyping and chromosomal microarray analysis (CMA) were performed for the patient and his parents.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>Clinical 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.</p>

Phenotypic and genetic analysis of a patient presented with Tietz/Waardenburg type II a syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the genetic cause for a patient featuring decreased pigmentation of the skin and iris, hearing loss and multiple congenital anomalies.</p><p><b>METHODS</b>Routine chromosomal banding was performed to analyze the karyotype of the patient and his parents. Single nucleotide polymorphism array (SNP array) was employed to identify cryptic chromosome aberrations, and quantitative real-time PCR was used to confirm the results.</p><p><b>RESULTS</b>Karyotype analysis has revealed no obvious anomaly for the patient and his parents. SNP array analysis of the patient has demonstrated a 3.9 Mb deletion encompassing 3p13p14.1, which caused loss of entire MITF gene. The deletion was confirmed by quantitative real-time PCR. Clinical features of the patient have included severe bilateral hearing loss, decreased pigmentation of the skin and iris and multiple congenital anomalies.</p><p><b>CONCLUSION</b>The patient, carrying a 3p13p14.1 deletion, has features of Tietz syndrome/Waardenburg syndrome type IIa. This case may provide additional data for the study of genotype-phenotype correlation of this disease.</p>

Phenotypic and genetic analysis of a child with blepharophimosis, ptosis, epicanthus inverses syndrome and tetralogy of Fallot / 中华医学遗传学杂志

OBJECTIVE To determine the genetic cause of a child with blepharophimosis, ptosis, and epicanthus inverses syndrome and tetralogy of Fallot, and to correlate the phenotype with the genotype. METHODS Routine G-banding has been previously performed on the patient and her parents. Chromosome microarray analysis (CMA) was performed for the three individuals and the fetus. RESULTS Chromosomal analysis has suggested normal karyotypes for the child and her parents. However, a de novo 8.9 Mb deletion on chromosome 3q22.1-q23 was detected by CMA. The deleted region has encompassed 74 genes including 41 disease-related genes, and this is also the most frequent region involved in interstitial 3q deletion. Patients with deletion of this region often have a common feature of dysplasia of eyelids, as well as a spectrum of other anomalies according to different breakpoints, including microcephaly, skeletal anomalies, congenital heart defects, cranial anomalies, intellectual disability and developmental delay. The patient's phenotype was in accordance with such spectrum. Her parents and sib did not show this variation by CMA. CONCLUSION The de novo interstitial deletion of 3q22.1-q23 probably underlies the main clinical manifestation in this child. CMA can provide more detailed information and allow further investigation of the genotype-phenotype correlation.

Comparison of results of improved FISH and conventional karyotyping analysis of 2607 amniotic fluid samples / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To compare the results of fluorescence in situ hybridization (FISH) assay and conventional karyotyping analysis for the detection of chromosomal aneuploidies.</p><p><b>METHODS</b>In total 2607 amniotic fluid samples were subjected to an improved FISH technique. Meanwhile, karyotype analysis was also ordered for each sample.</p><p><b>RESULTS</b>Of 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.</p><p><b>CONCLUSION</b>For 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.</p>

Clinical characterization of a Korean case with 3p25 deletion

Chromosome 3 (3p) deletion syndrome is a rare genomic disorder caused by a deletion at the terminal end of the short arm of chromosome 3. The primary characteristics of the syndrome are delayed development, dysmorphic features, and several other congenital anomalies. Here, we describe the case of a 2-year-old Korean girl with typical features of 3p deletion syndrome, including dysmorphic facial features, low birth weight, developmental delay, growth and cognitive retardation, and congenital heart disease. This case represents the first report of 3p deletion syndrome in Korea. Although phenotypes can be variable among patients, a clinically recognizable pattern has been described for this genetic defect, and our report helps to identify other cases with 3p deletion syndrome from a clinical and genetic perspective.

Clinicopathologic features of clear cell papillary renal cell carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathological features, differential diagnosis and prognosis of clear cell papillary renal cell carcinoma (CCPRCC).</p><p><b>METHODS</b>The histological, immunohistochemical, and molecular features were studied in 11 cases and follow-up data were also analyzed.</p><p><b>RESULTS</b>There were a total of 3 females and 8 males. The age of patients were ranged from 33 to 72 years(mean age 52.5 years). The diameters of tumors varied from 1cm to 4 cm. Histologically, papillary and cystic architecture were present at least focally in all tumors. The papillae were covered by small to medium-sized cuboidal cells with abundant clear cytoplasm and often showed extensive secondary branching, which were often folded and densely packed, resulting in a solid appearance. The nuclei were round and uniform in shape; nucleoli were not prominent (Fuhrman grade 1 or 2). Neither mitotic figures nor necrosis was present. All 11 cases exhibited moderate to strong positivity for CK7, CA9, vimentin, and HIF-1α, coupled with negative reactions for CD10, P504S, and TFE3. Ksp-cadherin was positively expressed in 8 cases.VHL gene mutations were not found in all 11 cases. Losses of chromosomes 3 (monoploid chromosome 3) was detected in 3 cases.</p><p><b>CONCLUSIONS</b>CCPRCC is uncommon and seemed to be an indolent tumor. The differential diagnosis should be included tumors, which harbor clear cell and papillary structure including clear cell renal cell carcinoma, papillary renal cell carcinoma, Xp11 translocation renal cell carcinoma, and CCPRCC. Immunohistochemical and molecular analysis may be help for its diagnosis.</p>

Derivative chromosome 11 in a child resulting from a complex rearrangement involving chromosomes 3, 6 and 11 in father: Significance of parental karyotyping.

The presence of derivative chromosome in a child with phenotypic features necessitates the need of parental karyotyping to ascertain the exact amount of loss or gain of the genetic material. The aim of this study was to emphasize the importance of parental karyotyping. Cytogenetic evaluation of the proband and his father were carried out at Laboratory. Cytogenetic analysis was performed on phytohemagglutinin stimulated cultures. The derivative chromosome 11 in proband was ascertained to have additional material from chromosome 6p arising from complex chromosomal rearrangement in the father. Karyotyping is the basic, cost-effective preliminary investigation in a child with mental subnormality or congenital anomalies.

Detection of RUNX1-MECOM Fusion Gene and t(3;21) in a Very Elderly Patient Having Acute Myeloid Leukemia with Myelodysplasia-Related Changes

An 87-yr-old woman was diagnosed with AML with myelodysplasia-related changes (AML-MRC). The initial complete blood count showed Hb level of 5.9 g/dL, platelet counts of 27x10(9)/L, and white blood cell counts of 85.33x10(9)/L with 55% blasts. Peripheral blood samples were used in all the tests, as bone marrow examination could not be performed because of the patient's extremely advanced age and poor general health condition. Flow cytometric analysis, chromosome analysis, FISH, and reverse transcriptase-PCR (RT-PCR) results indicated AML-MRC resulting from t(3;21) with the RUNX1-MECOM fusion gene. To our knowledge, this is the second most elderly de novo AML patient associated with t(3;21) to be reported.

A case of partial trisomy 3p syndrome with rare clinical manifestations / 소아과

Partial trisomy 3p results from either unbalanced translocation or de novo duplication. Common clinical features consist of dysmorphic facial features, congenital heart defects, psychomotor and mental retardation, abnormal muscle tone, and hypoplastic genitalia. In this paper, we report a case of partial trisomy 3p with rare clinical manifestations. A full-term, female newborn was transferred to our clinic. She had cleft lip-plate, dysgenesis of the corpus callosum, patent ductus arteriosus, pulmonary hypertension, and severe right-sided hydronephrosis, associated with ureteropelvic junction obstruction. Cytogenetic investigation revealed partial trisomy 3p; 46,XX,der(4)t(3;4) (p21.1;p16). The karyotype of her father showed a balanced translocation, t(3;4)(p21.1;p16). Therefore, the size of duplication can be an important factor.

A case of partial trisomy 3p syndrome with rare clinical manifestations / 소아과

Partial trisomy 3p results from either unbalanced translocation or de novo duplication. Common clinical features consist of dysmorphic facial features, congenital heart defects, psychomotor and mental retardation, abnormal muscle tone, and hypoplastic genitalia. In this paper, we report a case of partial trisomy 3p with rare clinical manifestations. A full-term, female newborn was transferred to our clinic. She had cleft lip-plate, dysgenesis of the corpus callosum, patent ductus arteriosus, pulmonary hypertension, and severe right-sided hydronephrosis, associated with ureteropelvic junction obstruction. Cytogenetic investigation revealed partial trisomy 3p; 46,XX,der(4)t(3;4) (p21.1;p16). The karyotype of her father showed a balanced translocation, t(3;4)(p21.1;p16). Therefore, the size of duplication can be an important factor.

Tumor suppressor genes on frequently deleted chromosome 3p in nasopharyngeal carcinoma / 癌症

Nasopharyngeal carcinoma (NPC) is among the most common malignancies in southern China. Deletion of genomic DNA, which occurs during the complex pathogenesis process for NPC, represents a pivotal mechanism in the inactivation of tumor suppressor genes (TSGs). In many circumstances, loss of TSGs can be detected as diagnostic and prognostic markers in cancer. The short arm of chromosome 3 (3p) is a frequently deleted chromosomal region in NPC, with 3p21.1-21.2 and 3p25.2-26.1 being the most frequently deleted minimal regions. In recent years, our research group and others have focused on the identification and characterization of novel target TSGs at 3p, such as RASSF1A, BLU, RBMS3, and CHL1, in the development and progression of NPC. In this review, we summarize recent findings of TSGs at 3p and discuss some of these genes in detail. A better understanding of TSGs at 3p will significantly improve our understanding of NPC pathogenesis, diagnosis, and treatment.

CD5-negative Blastoid Variant Mantle Cell Lymphoma with Complex CCND1/IGH and MYC Aberrations

The coexistence of CCND1/IGH and MYC rearrangements in mantle cell lymphoma (MCL) is a rare finding associated with a very poor prognosis. In this study, a patient with blastoid variant (MCL) is reported. The disease was clinically aggressive and refractory to chemotherapy, and the patient only survived for 1 month following diagnosis. Conventional cytogenetic study, FISH, and multicolor FISH (mFISH) demonstrated the involvement of the BCL1/CCND1 locus in a complex translocation, t(3;11)(q25;p15)t(11;14)(q13;q32). In addition, subclonal abnormalities in the 8q24 region, manifested as a t(8;14)(q24;q32)/MYC rearrangement, were identified. To the best of our knowledge, this is the first MCL case in Korea bearing these complex genomic aberrations.

Molecular genetics of functional articulation disorder in children / 中国当代儿科杂志

Genetic factors are an important cause of functional articulation disorder in children. This article reviews some genes and chromosome regions associated with a genetic susceptibility to functional articulation disorders. The forkhead box P2 (FOXP2) gene on chromosome 7 is introduced in details including its structure, expression and function. The relationship between the FOXP2 gene and developmental apraxia of speech is discussed. As a transcription factor, FOXP2 gene regulates the expression of many genes. CNTNAP2 as an important target gene of FOXP2 is a key gene influencing language development. Functional articulation disorder may be developed to dyslexia, therefore some candidate regions and genes related to dyslexia, such as 3p12-13, 15q11-21, 6p22 and 1p34-36, are also introduced. ROBO1 gene in 3p12.3, ZNF280D gene, TCF12 gene, EKN1 gene in 15q21, and KIAA0319 gene in 6p22 have been candidate genes for the study of functional articulation disorder.