Child ; Humans ; Chromosomes, Human, Pair 16 ; Leukemia, Myeloid, Acute ; Neoplasms, Multiple Primary/genetics* ; Oncogene Proteins, Fusion/genetics* ; RNA-Binding Protein FUS/genetics* ; Sarcoma, Myeloid/genetics* ; Transcriptional Regulator ERG/genetics* ; Translocation, Genetic

OBJECTIVE: To review the clinical data of a fetus with false positive result of non-invasive prenatal testing (NIPT) due to confined placental mosaicism (CPM). METHODS: Amniotic fluid sample was taken from a pregnant women with high risk for chromosome 16 aneuploidy for karyotyping analysis, single nucleotide polymorphism array (SNP array) and interphase fluorescence in situ hybridization (FISH). Genetic testing was also conducted on the fetal and maternal surface of the placenta, root of umbilical cord and fetal skin tissue after induced abortion. RESULTS: Cytogenetic analysis of the amniotic fluid sample yielded a normal karyotype. SNP array revealed mosaicism (20%) of trisomy 16 in the fetus. FISH confirmed the presence of mosaicism (25%) for trisomy 16. After induced labor, all sampled sites of placenta were confirmed to contain trisomy 16 by SNP array, while the analysis of fetal skin tissue yielded a negative result. CONCLUSION CPM is an important factor for false positive NIPT result. Prenatal identification of CPM and strengthened pregnancy management are important to reduce adverse pregnancy outcomes.
Amniocentesis ; Chromosomes, Human, Pair 16/genetics* ; Cytogenetic Analysis ; Female ; Fetus ; Humans ; In Situ Hybridization, Fluorescence ; Molecular Biology ; Mosaicism ; Placenta ; Pregnancy ; Prenatal Diagnosis ; Trisomy/genetics*

OBJECTIVE: To explore the genetic basis for a child featuring developmental delay, intelligent disability and language deficit. METHODS: Peripheral blood samples of the child and her parents were collected for routine G-banding karyotyping analysis and single nucleotide polymorphism array (SNP array) detection. Amniotic fluid was also sampled from the mother for karyotyping analysis and SNP array detection. RESULTS: No karyotypic abnormality was found with the child and her parents. SNP array showed that the child has carried a 761.4 kb microdeletion at 16p11.2, while her mother has carried a 444.4 kb microduplication at 15q13.3. Her father's result was negative. Further analysis showed that the 15q13.3 microduplication was inherited from her maternal grandfather who was phenotypically normal. Prenatal diagnosis showed that the fetus has inherited the15q13.3 microduplication from its mother. CONCLUSION The child has carried a de novo 16p11.2 microdeletion, which overlaps with 16p11.2 microdeletion syndrome region, in addition with similar clinical phenotypes. The 16p11.2 microdeletion probably underlies her abnormal phenotype.
Child ; Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 16 ; Developmental Disabilities/genetics* ; Female ; Fetus ; Humans ; Karyotyping ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis

OBJECTIVETo identify the genetic cause for a 11-year-old Chinese boy with Meier-Gorlin syndrome (MGS).

METHODSChromosomal microarray analysis (CMA) was used to detect potential variations, while whole exome sequencing (WES) was used to identify sequence variants. Sanger sequencing was used to confirm the suspected variants.

RESULTSThe boy has featured short stature, microtia, small patella, slender body build, craniofacial anomalies, and small testes with normal gonadotropin. A complete uniparental disomy of chromosome 16 was revealed by CMA. WES has identified a novel homozygous mutation c.67A>G (p.Lys23Glu) in ORC6 gene mapped to chromosome 16. As predicted by Alamut functional software, the mutation may affect the function of structural domain of the ORC6 protein.

CONCLUSIONThe patient is probably the first diagnosed MGS case in China, who carried a novel homozygous mutation of the ORC6 gene and uniparental disomy of chromosome 16. The effect of this novel mutation on the growth and development needs to be further investigated.

Base Sequence ; Child ; Chromosomes, Human, Pair 16 ; genetics ; Congenital Microtia ; genetics ; Family Health ; Fathers ; Growth Disorders ; genetics ; Heterozygote ; Humans ; Male ; Micrognathism ; genetics ; Mutation ; Origin Recognition Complex ; genetics ; Patella ; abnormalities ; Polymerase Chain Reaction ; methods ; Sequence Analysis, DNA ; methods ; Uniparental Disomy ; genetics

The clinical manifestations of five children with paroxysmal kinesigenic dyskinesia (PKD) were retrospectively analyzed and their gene mutations were analyzed by high-throughput sequencing and chromosome microarray. The 5 patients consisted of 4 males and 1 female and the age of onset was 6-9 years. Dyskinesia was induced by sudden turn movement, scare, mental stress, or other factors. These patients were conscious and had abnormal posture of unilateral or bilateral extremities, athetosis, facial muscle twitching, and abnormal body posture. The frequency of onset ranged from 3-5 times a month to 2-7 times a day, with a duration of <30 seconds every time. Electroencephalography showed no abnormality in these patients. Three patients had a family history of similar disease. The high-throughput sequencing results showed that a heterozygous mutation in the PRRT2 gene, c.649_650insC (p.R217PfsX8), was found in two patients; the mutation c.436C>T (p.P146S) was found in one patient; a splice site mutation, IVS2-1G>A, was found in one patient. The two mutations c.436C>T and IVS2-1G>A had not been reported previously. The chromosome microarray analysis was performed in one patient with negative results of gene detection, and the chromosome 16p11.2 deletion (0.55 Mb) was observed. Low-dose carbamazepine was effective for treatment of the 5 patients. PKD is a rare neurological disease. The detection of the PRRT2 gene by multiple genetic analysis can help the early diagnosis of PKD.
Carbamazepine ; therapeutic use ; Child ; Chromosome Deletion ; Chromosomes, Human, Pair 16 ; Dystonia ; complications ; diagnosis ; drug therapy ; genetics ; Electroencephalography ; Female ; Humans ; Male ; Membrane Proteins ; genetics ; Mutation ; Nerve Tissue Proteins ; genetics

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 determine the genetic cause for a boy with development delay and multiple congenital anomalies.

METHODSRoutine chromosomal banding was performed to analyze the karyotype of the patient and his parents. Single nucleotide polymorphism array (SNP array) was employed to investigate cryptic chromosome aberrations, and quantitative real-time PCR (qPCR) was used to confirm the result.

RESULTSKaryotype analysis revealed no obvious anomaly for the patient and his parents. The karyotype of the patient was 46,XY. SNP array has detected an 846 kb deletion at 16p13.11, which was verified by qPCR. Clinical features of the patient included development delay, distinct facial dysmorphism and multiple congenital anomalies.

CONCLUSIONA case of 16p13.11 microdeletion syndrome was identified. The deletion was probably induced by non-allelic homologous recombination (NAHR) at 16p13.11. SNP array and qPCR were helpful for the discovery of the microdeletion and have played an important role in the diagnosis and genetic counseling of the patient.

Abnormalities, Multiple ; genetics ; Chromosome Deletion ; Chromosomes, Human, Pair 16 ; Humans ; Infant ; Intellectual Disability ; genetics ; Karyotyping ; Male ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide

KBG syndrome is a very rare genetic disorder characterized by macrodontia of upper central incisors, global developmental delay, distinctive craniofacial features, short stature, and skeletal anomalies. Ankyrin repeat domain 11 gene (ANKRD11) has recently been identified as a causal factor of this syndrome. We describe a 6-yr-old Korean boy with features of KBG syndrome. The patient had a short stature, macrodontia, dysmorphic facial features, speech and motor delay with intellectual disability, and partial seizures as indicated by the electroencephalogram, but he was neither autistic nor had autism spectrum disorders. Using high-resolution oligonucleotide array comparative genomic hybridization, we identified a heterozygous 240-kb deletion at 16q24.3 corresponding to ANKRD11. This patient provided additional evidence on the influence of ANKRD11 in KBG syndrome and suggested that deletion limited to ANKRD11 is unlikely to cause autism.
Abnormalities, Multiple/diagnosis/*genetics ; Asian Continental Ancestry Group/*genetics ; Bone Diseases, Developmental/diagnosis/*genetics ; Child ; Chromosomes, Human, Pair 16 ; Comparative Genomic Hybridization ; Electroencephalography ; Facies ; Gene Deletion ; Heterozygote ; Humans ; Intellectual Disability/diagnosis/*genetics ; Male ; Phenotype ; Repressor Proteins/*genetics ; Republic of Korea ; Tooth Abnormalities/diagnosis/*genetics

This study was undertaken to identify genetic polymorphisms that are associated with the risk of an elevated fasting glucose (FG) level using genome-wide analyses. We explored a quantitative trait locus (QTL) for FG level in a genome-wide study from a Korean twin-family cohort (the Healthy Twin Study) using a combined linkage and family-based association analysis approach. We investigated 1,754 individuals, which included 432 families and 219 pairs of monozygotic twins. Regions of chromosomes 2q23.3-2q31.1, 15q26.1-15q26.3, 16p12.1, and 20p13-20p12.2, were found to show evidence of linkage with FG level, and several markers in these regions were found to be significantly associated with FG level using family-based or general association tests. In particular, a single-nucleotide polymorphism (rs6138953) on the PTPRA gene in the 20p13 region (combined P = 1.8 x 10(-6)) was found to be associated with FG level, and the PRKCB1 gene (in 16p12.1) to be possibly associated with FG level. In conclusion, multiple regions of chromosomes 2q23.3-2q31.1, 15q26.1-15q26.3, 16p12.1, and 20p13-20p12.2 are associated with FG level in our Korean twin-family cohort. The combined approach of genome-wide linkage and family-based association analysis is useful to identify novel or known genetic regions concerning FG level in a family cohort study.
Adult ; Aged ; Asian Continental Ancestry Group/*genetics ; Blood Glucose/*genetics ; Chromosomes, Human, Pair 15/genetics ; Chromosomes, Human, Pair 16/genetics ; Chromosomes, Human, Pair 2/genetics ; Chromosomes, Human, Pair 20/genetics ; Cohort Studies ; Family ; Female ; *Genetic Linkage ; *Genome-Wide Association Study ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Protein Kinase C/genetics ; Quantitative Trait Loci ; Receptor-Like Protein Tyrosine Phosphatases, Class 4/*genetics ; Republic of Korea ; Twins, Monozygotic/*genetics

OBJECTIVETo evaluate the clinical and laboratory features of pediatric inv(16) acute myeloid leukemia (AML) retrospectively.

METHODDual color fluorescence in situ hybridization (D-FISH) using a LSI CBFβ inv(16) break apart probe labeled by Spectrum red and Spectrum green was performed in 15 acute myeloid leukemia cases, including 13 cases with or without abnormal eosinophils but with positive core binding factor β (CBFβ)-MYH11 fusion transcript detected by RT-PCR, and 2 cases with trisomy 8 (+8). The results were compared with the morphology, immunophenotype, karyotype and RT-PCR.

RESULTMorphologically, 12 cases were diagnosed as M(4)EO, 2 as M(4), and 1 as M(2a). Immunophenotypically, all 13 AML cases with inv(16) showed positive expression of CD(13) and CD(33), but without the expression of any lymphoid lineage antigens. Karyotyping analysis with G-banding detected inv(16) in 10 AML cases, including 9 M(4)EO cases and 1 M(2a), but only 5 positive cases were detected using R-banding technique. Among them, 2 cases had simultaneous +8 and trisomy22 (+22), one had +22 only in addition to inv(16). D-FISH revealed a CBFβ-MYH11 rearrangement in 13 cases of AML with positive RT-PCR results, and the mean positive rate of cell detection was 55.15% (range 37.0% - 86.0%). The complete remission rate (CR) and median survival period in this series of inv(16) AML were 81.5%and 11 months, respectively, of whom, 8 cases were still in CR. Relapse and karyotypic evolution were seen in case 5 with +8, +22 in addition to inv(16).

CONCLUSIONAML with inv(16) is a special subtype. Most cases belong to M(4)EO. Its prognosis is good in general, but it seems to be an unfavorable feature for AML with inv(16) and +8, +22 simultaneously, especially with karyotypic evolution. For detection of inv(16), G-banding technique is evidently superior to R-banding technique. D-FISH combined with RT-PCR are more sensitive and reliable than chromosome banding analysis.

Adolescent ; Child ; Child, Preschool ; Chromosome Deletion ; Chromosome Inversion ; Chromosomes, Human, Pair 16 ; genetics ; Eosinophilia ; pathology ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Infant ; Karyotyping ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; Male ; Prognosis ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction