OBJECTIVETo determine a complex chromosomal rearrangement by advanced molecular cytogenetic techniques and analyze its clinical effect.

METHODSA complex chromosomal rearrangement (CCR) involved in chromosomes 5, 16 and 20 in a 29-year-old male carrier was determined by chromosomal microdissection and multicolor fluorescence in situ hybridization (M-FISH), and family degree investigation was further performed.

RESULTSThe karyotype of the case was a complex chromosomal translocation among chromosomes 5, 20 and 16, and accompanied with a band of chromosome 20 inserted into chromosome 5. His mother and sister both had the same abnormal karyotype by familial investigation.

CONCLUSIONThe combined use of M-FISH and chromosome microdissection is a powerful tool to determine CCR. The complex chromosomal rearrangement could be transmitted stably in the family, but still the carriers could give birth to a healthy baby by chance.

Adult ; Chromosomes, Human, Pair 10 ; genetics ; Chromosomes, Human, Pair 16 ; genetics ; Chromosomes, Human, Pair 20 ; genetics ; Chromosomes, Human, Pair 5 ; genetics ; Cytogenetic Analysis ; methods ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Pregnancy ; Translocation, Genetic

OBJECTIVETo investigate global genetic alterations in medulloblastoma, and to localize critical chromosomal loci with allelic imbalances associated with the development of medulloblastoma.

METHODSA high-resolution genome-wide allelotype analysis, including 384 microsatellite markers, was performed in 12 medulloblastomas.

RESULTSAn average of 238 (62.3%) allelic imbalances were detected on all 39 autosomal arms. Non-random allelic gains or losses were detected on chromosomes 7q (58.3%), 8p (66.7%), 16q (58.3%), 17p (58.3%) and 17q (66.7%). In addition, chromosomal arms with frequencies of allelic imbalances higher than the mean percentage were identified on 3p (33.3%), 3q (33.3%), 4q (41.7%), 7p (33.3%), 8q (41.7%), 10q (41.7%), 13q (33.3%), 14q (33.3%) and 20q (33.3%). No relationship was found between the frequency of allelic imbalances and the clinical outcome of the patients.

CONCLUSIONSA global view of the genetic alterations in medulloblastoma was provided. The allelic imbalances involving chromosomes 7q, 8p, 16q, 17p and 17q may play an important role in the pathogenesis of medulloblastoma.

Adolescent ; Adult ; Alleles ; Allelic Imbalance ; Cerebellar Neoplasms ; genetics ; Child ; Child, Preschool ; Chromosomes, Human, Pair 16 ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 7 ; Chromosomes, Human, Pair 8 ; Female ; Genotype ; Humans ; Male ; Medulloblastoma ; genetics ; Microsatellite Repeats ; genetics

OBJECTIVETo explore the value of trisomy 22 ( +22) in the diagnosis of inv(16) acute myeloid leukemia (AML).

METHODSInterphase fluorescence in situ hybridization (FISH) was performed in 18 AML patients with +22. The probe was two-color break apart probe for CBFbeta with SpectrumRed on the centromeric side and SpectrumGreen on the telomeric side. The FISH results were compared with that of R-banding conventional cytogenetics (CC). Multiplex FISH (M-FISH) was used to analyze the relationship of +22 and inv(16).

RESULTSCC revealed inv(16) in none of the 18 AML, with +22, but FISH revealed inv (16) in 11 of them and del( 16) (q22) in one. As CC results, 9 of the 11 cases were sole +22, one complicated with trisomy 8, and one del(16) (q22). Four patients with +22 and inv(16) were analyzed by M-FISH and revealed +22 only.

CONCLUSION+22 can be regarded as an important marker for the diagnosis of inv(16) AML.

Adolescent ; Adult ; Aged ; Chromosome Inversion ; Chromosomes, Human, Pair 16 ; genetics ; Chromosomes, Human, Pair 22 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Trisomy

OBJECTIVETo report five cases of acute myeloid leukemia (AML) with t(16;21)(p11;q22) translocation and the result of chromosome painting analysis on one of them.

METHODSChromosome specimens were prepared by short-term culture of bone marrow cells. Karyotype analysis was made by R-banding technique. Chromosome painting was performed using whole chromosome probes 16 and 21 in 1 case.

RESULTSKaryotype analysis showed identical translocation t(16;21)(p11;q22) in all five cases, accounting for 0.3% of 1448 cases of acute myeoid leukemia examined in the past fifteen years. Moreover, chromosome painting distinctly demonstrated t(16;21) in one of them. Leukemia blasts did not show hemophagocytosis in all of them.

CONCLUSIONt(16;21) translocation is a rare and recurring chromosome rearrangement. It represents a specific type of AML. Chromosome painting technique is a more reliable means for detecting it, compared with the conventional karyotype analysis.

Acute Disease ; Adolescent ; Adult ; Cells, Cultured ; Child ; Chromosomes, Human, Pair 16 ; genetics ; Chromosomes, Human, Pair 21 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Leukemia, Myeloid ; genetics ; Male ; Translocation, Genetic

OBJECTIVETo evaluate fluorescence in situ hybridization (FISH) in the detection of inv (16) (p13; q22).

METHODSSpectrum red labeled yeast artificial chromosome (YAC) clone 854E2 which spans the breakpoint cluster region in MYH11 in band 16p13 and single color interphase FISH were used to detect inv (16) in 26 cases of acute myelomonocytic leukemias (AML-M(4)), and the results were compared with that of conventional cytogenetic analysis.

RESULTSR banding karyotyping test revealed no inv (16) in 25 cases, one AML M(4Eo) case showed inv (16) by G banding. Nine cases including all three M(4Eo) had inv (16) by FISH analysis, among whom the characteristic fluorescence signal pattern of the inv (16) was seen in 13.3% to 32.1% (median, 21.3%) of the tested cells.

CONCLUSIONYAC 854E2 and interphase FISH provide a powerful technique in the detection of inv (16) (p13q22).

Adult ; Aged ; Chromosome Inversion ; Chromosomes, Human, Pair 16 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Interphase ; genetics ; Leukemia, Myelomonocytic, Acute ; genetics ; pathology ; Male ; Middle Aged

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

Adolescent ; Adult ; Aged ; Cerebellar Neoplasms ; genetics ; Child ; Child, Preschool ; Chromosomes, Human, Pair 16 ; Female ; Humans ; Loss of Heterozygosity ; Male ; Medulloblastoma ; genetics ; Middle Aged

To study the clinical significance of the detection of inv(16) (p13 q22) by FISH in the diagnosis and prognosis for M(4), the metaphase bone marrow cells of 6 cases M(4) which had already diagnosed by morphology were detected for CBFbeta-MYH(11) fusion gene by MYH 11 probe including dual labelled sequences and the results were compared with that of conventional cytogenetic analysis. The results showed that 4 cases inv(16) (two M(4) EO and two M(4)) were found by G banding kanyotyping test. One case M(4) had trisomy (+22) in addition to inv(16); one case M(4) had hypodiploid in addition to inv(16), which relapsed after CR 8 months. All 6 cases had inv(16) abnormal fluorescence signal. Among them case No 2 had the deletion of 16p13 showed by red fluorescence signal in addition to inv(16). It is concluded that the detection of inv(16) by FISH is of sensitivity and specificity. It is the important supplement to the conventional cytogenetic analysis. It possesses the important clinical significance in the diagnosis and prognosis of M(4) patients.
Adolescent ; Adult ; Chromosome Inversion ; Chromosomes, Human, Pair 16 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Leukemia, Myelomonocytic, Acute ; genetics ; pathology ; Male ; Middle Aged ; Reproducibility of Results