OBJECTIVE: To explore the clinical and genetic characteristics of a boy with isolated maternal uniparental disomy of chromosome 20 [UPD(20)mat]. METHODS: A child who was admitted to the Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology on April 8,2021. was selected as the study subject. Phenotypic and endocrinological findings of the child were retrospectively analyzed. Whole exome sequencing (WES) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were carried out for detecting the UPD sequences and copy number variations. Both of his parents were verified by Sanger sequencing. Relevant literature was systematically reviewed. RESULTS: The child, a 3-year-and-8-month-old boy born to a 41-year-old mother by Cesarean delivery at 36⁺² gestational weeks due to oligohydramia, had a birth weight of 2 300 g and length of 46 cm. He was admitted to the NICU for feeding difficulties which had persisted despite of clinical management. At the age of 3.75, he had a height of 92.5 cm (< 3rd percentile; 25th ~ 50th percentile at 2.5 years) and a weight of 10.8 kg (< 3rd percentile; 50th percentile at 15 months). He had also presented with growth retardation, short stature, attention deficit and hyperactivity disorder (ADHD), mild mental retardation, and speech and language development disorders. He had simian creases in both hands but no additional dysmorphic signs, and his motor development was normal. Serum insulin, thyroid-stimulating hormone, and insulin growth factor binding protein 3 levels were within the normal ranges, though insulin growth factor-1 (IGF-1) was slightly decreased. Since that time he had continuously used atomoxetine hydrochloride capsules to control his ADHD. WES and MS-MLPA revealed the existence of UPD (20)mat. CONCLUSION The UPD(20)mat syndrome is characterized by feeding difficulties, growth retardation and short stature. The child in our case has been accompanied by ADHD and speech and language development disorders, which required long-term treatment. For women with advanced maternal age and suggestive phenotypes, genetic testing and counseling should be conducted.
Male ; Pregnancy ; Humans ; Child ; Female ; Infant ; Adult ; Chromosomes, Human, Pair 20 ; DNA Copy Number Variations ; Retrospective Studies ; Uniparental Disomy/genetics* ; Atomoxetine Hydrochloride ; Dwarfism ; Intercellular Signaling Peptides and Proteins ; Language Development Disorders ; Growth Disorders ; Insulins

OBJECTIVE: To explore the clinical features and therapeutic efficacy in adult ALL patients with t (1; 19) (E2A-PBX1). METHODS: The clinic data of 19 adult ALL patients with t (1; 19) (E2A-PBX1) in our hospital from Nov. 22, 2010 to Apr. 4, 2018 were collected. The clinical features,complete remission (CR) rate, overall survival (OS) rate and relapse-free survival (RFS) rate of patients received chemotherapy and chemotherapy+HSCT were analyzed. RESULTS: In all the 19 patients, the median age was 24 (14-66), median WBC count was 16.47×109 (1.8-170.34)/L, median Hb level was 98 (65-176) g/L, median Plt count was 50 (15-254)×109/L. Pre B-ALL were 17 cases (89.5%), and common B-ALL were 2 cases (10.5%). Patients received the induction therapy, the overall CR rate was 94.7%, one course CR rate was 94.7%, 4 year OS rate was 47.1% and RFS rate was 43.3%. The OS rate and RFS rate of patients received transplantation were slightly higher than those of patients not received transplantation (OS: 62.5% vs 36.7%) (P=0.188)；RFS (62.5% vs 38.9%) (P=0.166). CONCLUSION Most adult ALL patients with t (1; 19) (E2A-PBX1) is Pre B-ALL by Immunophenotyping, as compared with the pediatric patients, the therapeutic efficacy for adult patients with t (1; 19) (E2A-PBX1) is worsen, therefore, stem cell transplantation is still acquired for better long term survival.
Adult ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 19 ; Homeodomain Proteins ; genetics ; Humans ; Immunophenotyping ; Oncogene Proteins, Fusion ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; therapy ; Recurrence ; Remission Induction

Chromosomal loss in trisomy (trisomy rescue) to generate a disomic fetus can cause confined placental mosaicism and/or feto/placental mosaicism. After trisomy rescue event, there is a risk of fetal uniparental disomy (UPD). Noninvasive prenatal test (NIPT) reflects the genomic constitution of the placenta, not of the fetus itself. Feto-placental discrepancy can therefore cause false-positive (trisomy) NIPT results. These discordant NIPT results can serve as important clues to find UPD associated with confined placental mosaicism. We report a case with maternal UPD of chromosome 20, detected by NIPT of 1,000 high-risk pregnancies, carried out for detecting chromosomal abnormalities in Koreans.
Chromosome Aberrations ; Chromosomes, Human, Pair 20* ; Constitution and Bylaws ; Fetus ; Mosaicism ; Placenta ; Pregnancy, High-Risk* ; Trisomy ; Uniparental Disomy*

Pseudohypoparathyroidism type 1b (PHP 1b) is the result of end organ resistance to parathyroid hormone (PTH) in the absence of any features of Albright's hereditary osteodystrophy. There are two subtypes of PHP 1b with different genetic mechanisms. One subtype is related to a maternally derived 3kb microdeletion involving STX 16 gene, and is inherited in an autosomal dominant mode. Familial autosomal dominant inheritance of PHP 1b is relatively rare. The other subtype is associated with more extensive loss of imprinting at the GNAS locus that affects at least one additional differential methylated (hypermethylation at neuroendocrine secretory protein and hypomethylation at antisense transcript and or extra-large stimulatory G protein region) without microdeletion of the STX 16 or AS gene. It can be sporadic due to an imprinting defect in the GNAS gene. In our case, an 8-year-old girl was referred for suspected PHP with no feature of Albright hereditary osteodystrophy. Blood test results revealed hypocalcemia and hyperphosphatemia. Elevated PTH was also checked. There was no family history of endocrine or developmental problem. Her intelligence was normal, but she had inferior sociability at that time. Based on above, we diagnosed a rare case of paternal uniparental disomy of the long arm of chromosome 20 as the cause of PHP 1b by microsatellite marker test of chromosome 20.
Arm ; Child ; Chromosomes, Human, Pair 20 ; Female ; GTP-Binding Proteins ; Hematologic Tests ; Humans ; Hyperphosphatemia ; Hypocalcemia ; Intelligence ; Microsatellite Repeats ; Parathyroid Hormone ; Pseudohypoparathyroidism* ; Uniparental Disomy* ; Wills

Only 6 patients with partial trisomy of the long arm of chromosome 19 (19q), caused by direct interstitial duplications, have been reported until today. Herein, we report a pediatric patient with a novel 1.13 Mb direct interstitial duplication within 19q13.32, which is the smallest fragment affected so far. A five-year old Korean boy of healthy parents presented with microcephaly, growth retardation, developmental delay, and craniofacial dysmorphism. Even though G-banded chromosome analysis at resolution of 550-band revealed normal karyotype, duplication of 1.13 Mb fragment within 19q13.32 was detected by array comparative genomic hybridization. Comparing with previously reported patients with pure duplication involving 19q as a sole chromosomal abnormality, our case showed the smallest duplication segment with relatively mild degree of clinical features. Our present case might serve as the landmark case among patients with 19q duplication for genotype-phenotype correlation study and further identification of critical region for 19q duplication abnormalities.
Arm ; Asian Continental Ancestry Group* ; Chromosome Aberrations ; Chromosomes, Human, Pair 19 ; Comparative Genomic Hybridization ; Genetic Association Studies ; Humans ; Karyotype ; Male ; Microcephaly* ; Parents ; Trisomy

OBJECTIVETo determine the genetic cause for two mentally retarded patients from a family, and to correlate their genotypes with clinical phenotypes.

METHODSRoutine G-banded karyotyping analysis was performed. Single nucleotide polymorphism (SNP) microarray analysis was used to detect microdeletions or microduplications. Fluorescence in situ hybridization (FISH) was used to ascertain the origin of chromosomal abnormalities.

RESULTSBoth proband and his uncle showed a normal karyotype. SNP microarray analysis has identified a 1.147-Mb microdeletion at 16p13.3 (85 880-1 233 819) and a 2.948-Mb microduplication at 19q13.42-q13.43 (56 008 597-58 956 816). FISH analysis confirmed that the patient has inherited a derivative chromosome 16 from his father. The proband presented with mental retardation, reduced speech, and facial dysmorphism (hypertelorism, down-slanting palpebral fissure, low nasal bridge and wide gap between front teeth). His uncle presented with a milder phenotype with mental retardation.

CONCLUSIONBoth the proband and his uncle have carried a chromosome microdeletion at 16p and microduplication at 19q, which were originated from their fathers carrying a balanced t(16;19) translocation. Combined SNP microarray analysis and FISH assay are useful for the detection the copy number variations and delineation of potential structural changes, which may help with evaluation of recurrence risk for this family.

Adult ; Child ; Chromosome Deletion ; Chromosome Duplication ; Chromosomes, Human, Pair 16 ; Chromosomes, Human, Pair 19 ; Humans ; In Situ Hybridization, Fluorescence ; Intellectual Disability ; genetics ; Karyotyping ; Male ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide ; Translocation, Genetic

OBJECTIVETo assess the association of 8 single nucleotide polymorphisms (SNPs) from chromosomes X and 20 with androgenetic alopecia among ethnic Han population from Yunnan province.

METHODSAn eight-SNP co-amplification protocol was developed for the genotyping with a SNaPshot platform. A case-control study was carried out for the 8 SNPs from chromosomes X and 20 in 115 androgenetic alopecia cases and 125 healthy controls. Statistical analysis was conducted with SPSS17.0, Haploview4.2, SHEsis and MDR software.

RESULTSNo association was found between the two groups with regard to the 4 SNPs located on the X chromosome. The genotypic frequencies of rs2180439, rs913063 and rs1160312 were significantly different between the two groups (P < 0.05). The frequency of T allele of rs2180439 was significantly higher in the case group (P < 0.05). The frequencies of A alleles of rs913063 and rs1160312 were significantly higher in the case group (P < 0.05). The haplotypes of C-T-C-G, T-C-C-G and T-T-A-A based on rs6137444-rs2180439-rs913063-rs1160312 showed significant difference between the two groups (P <0.05). rs6137444, rs21804393 and rs1160312 have a strong association with androgenetic alopecia.

CONCLUSIONThe 4 SNPs located on chromosome X were all monomorphic among ethnic Hans from Yunnan. The rs6152, rs16990427, rs1352015, rs1385699 SNPs located on chromosome 20 are associated with androgenetic alopecia in the same population. Individuals with T allele of rs2180439 and A allele of rs913063 and rs1160312 are more likely to develop androgenetic alopecia.

Adult ; Alopecia ; genetics ; Case-Control Studies ; China ; ethnology ; Chromosomes, Human, Pair 20 ; Chromosomes, Human, X ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

Non-coding expansion spinocerebellar ataxias (SCAs) are a group of autosomal dominant neurodegenerative diseases characterized by "CTA/CTG", "ATTCT", "TGGAA" expansion in non-coding region of the causative gene. Until now, 5 subtypes including SCA8, SCA10, SCA12, SCA31 and SCA36 have been mapped. Recently, the causative mutation for SCA36, namely intronic hexanucleotide GGCCTG expansion in NOP56 gene, has been identified in Japanese and Spanish pedigrees in succession. Compared with other subtypes of SCAs, there are certain distinctive characteristics for SCA36. The clinical and genetic features of SCA36 are reviewed in this paper.
Base Sequence ; Biomedical Research ; methods ; trends ; Chromosome Mapping ; Chromosomes, Human, Pair 20 ; genetics ; DNA Repeat Expansion ; genetics ; Genetic Predisposition to Disease ; genetics ; Humans ; Nuclear Proteins ; genetics ; Oligonucleotides ; genetics ; Spinocerebellar Ataxias ; genetics ; pathology

OBJECTIVETo investigate the clinicopathologic features and 19q13.42 gene changes in embryonal tumors with multilayered rosettes (ETMR).

METHODSImmunohistochemistry and fluorescence in situ hybridization (FISH) were performed in three ETMRs.

RESULTSThe average age of the patients were 34 months. Imaging revealed huge masses with inhomogeneous enhancement and two cases showed cystic lesions. Follow-up data showed 14 and 38 months survival in two children, the third had a recurrence 4 months after operation. Morphologically, the tumor was mainly composed of dense small primitive neuroepithelial cells in patchy or multilayer rosettes within a background of advanced neuronal differentiation, containing neurocytes, ganglion cells, and neuropil-like background. Immunohistochemical staining showed the neuronal marker, synaptophysin, was positive in differentiated areas. Nestin as a neural stem cell marker was immunoreactive in the primitive neuroepithelial cells including multilayered rosettes. Neurons with positive expression of NeuN were observed occasionally. Ki-67 index was up to 40%-80% in the undifferentiated cells and rosettes, but was only 1%-3% in the differentiated areas. CD99 was positive in perivascular papillary pattern areas in one case. 19q13.42 amplification was detected in more than 30% of tumor cells in all cases.

CONCLUSIONSETMR is a unique entity with distinctive clinical and pathological features. Chromosome 19q13.42 abnormality is valuable for confirming the diagnosis and for further treatment research.

Antigens, Nuclear ; genetics ; Child, Preschool ; Chromosomes, Human, Pair 19 ; genetics ; Genetic Testing ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Neoplasm Recurrence, Local ; Neoplasms, Germ Cell and Embryonal ; genetics ; pathology ; Nerve Tissue Proteins ; genetics ; Neuropil ; pathology ; Synaptophysin ; genetics

OBJECTIVETo correlate the presence of chromosome 1p/19q deletion with the expression of R132H mutant IDH1 status in oligodendroglial tumors, and to explore molecular markers for predicting chemosensitivity of oligodendroglial tumors.

METHODSThe study included 75 oligodendroglial tumors (38 oligodendrogliomas and 37 oligoastrocytomas). Immunohistochemistry was used to detect the expression of R132H mutant IDH1 protein, and fluorescence in situ hybridization (FISH) was employed to detect 1p/19q deletion.

RESULTSDeletion of chromosome 1p and/or 19q was detected in 37 cases (37/75, 49.3%), among which co-deletion of 1p and 19q was seen in 34 cases (closely correlated, P < 0.01). Oligodendrogliomas WHOIIhad a slightly higher deletion rate than oligodendrogliomas WHO III, although without statistical significance. Oligodendrogliomas WHO IIand WHO III had a significantly higher deletion rate of chromosome 1p/19q than oligoastrocytomas WHO II and WHO III (P < 0.05). While combined loss of 1p/19q was always detected in oligodendrogliomas when FISH was positive, isolated 1p or 19q deletion was only found in oligoastrocytomas. The expression of R132H mutant IDH1 was detected in 51 of 75 cases (68.0%), in which oligodendrogliomas had a higher positive rate than oligoastrocytomas. Statistical analysis demonstrated a significant correlation between the expression of R132H mutant IDH1 protein and the presence of combined 1p/19q deletion in oligodendrogliomas (P < 0.05).

CONCLUSIONSA significant correlation was observed between the expression of R132H mutant protein and 1p/19q LOH.Expression of 132H mutant IDH1 protein is the potential biomarker for predicating the presence of 1p/19q deletion in oligodendrogliomas.

Aged ; Brain Neoplasms ; genetics ; metabolism ; Chromosome Deletion ; Chromosomes, Human, 19-20 ; genetics ; Chromosomes, Human, Pair 1 ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Isocitrate Dehydrogenase ; genetics ; metabolism ; Middle Aged ; Mutant Proteins ; metabolism ; Neoplasm Proteins ; genetics ; metabolism ; Oligodendroglioma ; genetics ; metabolism