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(A) Karyotype of the fetus identified by GTG banding technique. (B) The father's karyotype. (C) The mother's karyotype.
Source publication
Rationale:
Chromosome deletion/duplication has been reported to be associated with mental disability and dysmorphism according to the accumulated research evidence.
Patient concerns:
A 25-year-old woman underwent amniocentesis for cytogenetic and single-nucleotide polymorphism (SNP) array analysis at 18 weeks of gestation due to the increased Do...
Contexts in source publication
Context 1
... fetus was initially found to have a seemingly normal karyotype of 46,XX by routine cytogenetic analysis ( Fig. ...
Context 2
... SNP array revealed a 17-Mb duplication of 4q34.1q35.2 and a 17-Mb deletion of 7q34q36.3 (4q34.1q35.2 [173,822,880,409] Â 3; 7q34q36.3 . 2C) both had normal chromosomal karyotypes. To further define the chromosome abnormalities were de novo or inherited from parental unbalanced translocation, the whole chromosome painting probes specific for chromosome 4 and 7 were applied subsequently. The chromosome 4 painting probe was found to hybridize to the terminal of chromosome 7q ...
Similar publications
Background
An STR locus with tri-allelic pattern is occasionally observed in routine forensic casework. The extra copy of TPOX locus with tri-allelic pattern in populations has been assumed to be inserted into an X chromosome, which took place forth before the Bantu expansion in Africa. Nonetheless, the exact location of the duplication and the for...
Citations
... We analysed a patient with a de novo~38Mb (38,242,408bps) pure, direct interstitial 4q duplication. Pure duplications of this kind are important in establishing phenotype-gene correlations (20). Other types of 4q duplications involving translocations with other chromosomes are not reliable cases to establish such correlations as the new location could influence the resulting phenotype (21). ...
We describe a sporadic case of a pure, tandem, interstitial chromosome 4q duplication, arr[hg19] 4q28.1q32.3 (127,008,069-165,250,477) x3 in a boy born at 36 weeks of gestation. He presented with microcephaly (head circumference <1st percentile), short stature (height <2nd percentile) and poor weight gain (weight <3rd percentile). Hypospadias and horseshoe shaped kidneys were also revealed following a urinary tract ultrasound. Biochemical analysis revealed normal growth hormone and thyroid hormone levels. While gross and fine motor skill development was in line with his age, speech delay was observed. This patient adds to a group of more than 30 cases of pure 4q tandem duplication with common and differing phenotypic presentations. Using a retrospective analysis of previous case studies alongside the current case and bioinformatics analysis of the duplicated region, we deduced the most likely dosage sensitive genes for some of the major phenotypes in the patient. The positive predictive value (PPV) was calculated for each gene and phenotype and was derived by comparing the previously reported patients who have gene duplications and an associated phenotype versus those who had the gene duplications but were unaffected. Thus, the growth retardation phenotype may be associated with NAA15 duplication, speech delay with GRIA2 and microcephaly with PLK4 duplication. Functional studies will help in confirming the observations and elucidating the mechanisms. However, our study highlights the importance of analysing case reports with pure duplications in defining phenotype-gene relationships and in improving our knowledge of the function of precise chromosomal regions.
... Some researchers believe that duplication of the 4q22-q23 correlates with renal hypoplsia [26], while a study conducted by Otsuka et al. [27] argued that renal hypoplasia might be female-prone and probably associate with the duplication of 4q33-q34 region. A recent study [28] with duplication of 4q34.1q35.2 reported their ultrasound findings of kidney abnormality, while a deletion of 7q34q36.3 was also observed [29]. In our research, the fetus in pedigree 1 had no renal substantial abnormality. ...
Aims
There is little knowledge about partial trisomy 4q and the genotype–phenotype correlation. In this study, we presented the detail of two Chinese families with partial distal 4q duplication in an attempt to clarify the correlation between the genotype and the phenotype.
Methods
Two pedigrees with distal 4q duplication were enrolled in this study. Karyotype analysis and single-nucleotide polymorphism (SNP) array detection were performed for prenatal diagnosis. Fluorescence in situ hybridization analysis. (FISH) was conducted to verify the copy number variants.
Results
Two families with partial trisomy 4q were identified. The fetus in pedigree 1 exhibited multiple ultrasound anomalies including intrauterine growth restriction and an atrioventricular septal defect who had a duplication of 4q28.3-qter associate with 6p25.2-p25.3 deletion, which resulted from balanced translocation carried by his father t(4;6)(q28.3;p25.2). The fetus in pedigree 2 had a distal 4q28.3-qter duplication combined with monosomy of Xp21.3-p22.3, and the karyotype was described as 46,X,der(X)t(X;4)(p21.3;q28.3)mat, which originally inherited from the pregnant woman who exhibited a mild clinical phenotype limited to short stature.
Conclusions
In our study, we for the first time identified the partial trisomy 4q associate with 6p or Xp deletion. In addition, our finding further strengthens that mild clinical phenotype in 4q duplication case may be due to the spreading of X inactivation to the autosomal in derivation of chromosome X.
... The final results were analyzed using Database of Chromosomal Imbalance and Phenotype in Humans using Ensemble Resources, Database of Genomic Variants, Online Mendelian Inheritance in Man (OMIM) and the National Center for Biotechnology Information. [10] ...
Rationale:
Chromosomal 3q deletion is a recurrent genomic alternation, which is rarely reported in clinic.
Patient concerns:
A 27-year-old woman underwent amniocentesis for cytogenetic analysis and single nucleotide polymorphism (SNP) array analysis at 27 weeks of gestation, due to ventricular septum defect in prenatal ultrasound findings.
Diagnoses:
G-banding analysis showed the karyotype of the fetus was normal and the couple also had normal karyotypes. However, SNP array detected a 1.71 Mb microdelection in 3q29, which was described as arr[hg19]3q29(194184392-195887205) × 1. There are 12 genes located in this locus.
Interventions:
The couple refused SNP array to testify the 3q29 microdeletion was inherited or de novo and they chose termination of pregnancy.
Outcomes:
The deleted region in the fetus overlapped with part 3q29 microdeletion syndrome, which was characterized by learning disability, speech delay, mental deficiency, ocular abnormalities and craniofacial features. In addition, no similar/overlapping 3q29 microdeletion cases were reported according to the published literature and database.
Lessons:
For the chromosomal microscopic imbalances partially overlapping with the defined pathogenic syndrome, deleted/duplicated size, genetic materials and phenotypic diversity should be taken into consideration when genetic counseling is offered by the clinicians.
... The collected image data were analyzed according to Illumina's Genome Studio software and the results were analyzed through the Database of Chromosomal Imbalance and Phenotype in Humans using Ensemble Resources (DECIPHER), database of genomic variants, Online Mendelian Inheritance in Man, National Center for Biotechnology Information, and so on. [12] ...
Introduction:
The infertile male individuals carrying the Y-autosome translocations are seldom reported in clinic. Herein, we described a severe oligozoospermic male with rare unbalanced Y;3 translocation transmitted through 3 generations.
Patient concerns:
A 33-year-old Chinese male was referred for infertility consultation in our center after 10 years' primary infertility. He was diagnosed as severe oligozoospermia according to the semen analysis.
Diagnosis:
G-banding analysis initially described the karyotype as 46, XY, add (3) (p26) for the patient, and his wife's karyotype was 46, XX. The chromosomal microarray analysis identified 3.81Mb and 0.29Mb duplications in Yq11.223q11.23 and Yq12, separately. No deletions were detected in azoospermia factors (AZF)a, AZFb and AZFc. Fluorescence in situ hybridization analysis further confirmed the existence of sex-determining region Y gene and verified that Yq12 was translocated to the terminal short arm of chromosome 3(3p26).
Interventions:
The couple chose intracytoplasmic sperm injection to get their offspring. The wife underwent amniocentesis for cytogenetic analysis but suffered termination of pregnancy due to premature rupture of membranes.
Outcomes:
The karyotype of the patient was finally described as 46, X, der(3)t(Y;3)(q11.22;p26). His father and the aborted fetus showed the same karyotypes as the patient.
Conclusion:
Our study not only enriched the karyotype-phenotype correlation of Y-autosome translocation, but also strengthened the critical roles of molecular genetic techniques in identifying the chromosomal breakpoints and regions involved.
Chromosomal aberrations may be numerical, due to the presence of an extra or missing chromosome, or structural, where there is a loss of a fragment, a supernumerary portion, or a reciprocal exchange of chromosome portions. There is often skeletal involvement in these syndromes. Whenever an anatomical abnormality of the foetus is present, it is necessary to request genetic testing because sometimes that single finding can allow a diagnosis characterized by severe functional handicaps. In addition, if we observe a growth retardation localized to certain districts or generalized, we must be aware that the prognosis is all the more serious the earlier this finding is made.
Duplications of 4q represent rare chromosomal abnormalities of variable clinical features, these being directly related to the size of the duplicated segment, and whether the change was isolated or with translocation of another chromosome. Anorectal anomalies are present in a wide spectrum of birth defects, and can be isolated or syndromic, with about 60% of affected patients also having other anomalies. We present in this report a case of anorectal anomaly diagnosed at birth associated with microcephaly, facial dysmorphisms and neuropsycho-motor developmental delay. It has a normal karyotype and with the aid of the CGH-array technique it was possi-ble to diagnose this case and expand the clinical phenotype of dup4q to include the association with anorectal anomaly.
Objective:
We present molecular cytogenetic characterization of del(X) (p22.33)mat and de novo dup(4) (q34.3q35.2) in a male fetus with multiple anomalies of facial dysmorphism, ventriculomegaly, congenital heart defects, short long bones and clinodactyly.
Case report:
A 36-year-old, gravida 3, para 1, woman with short stature (152 cm) underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,Y,del(X)(p22.33)mat, dup(4)(q34.3q35.2). The mother had a karyotype of 46,X,del(X)(p22.33). Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed arr Xp22.33 × 0, 4q34.3q35.2 × 3. Prenatal ultrasound at 23 weeks of gestation revealed multiple anomalies of flat nasal bridge, ventriculomegaly, atrioventricular septal defect (AVSD) and clinodactyly. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial dysmorphism. Cytogenetic analysis of the umbilical cord revealed 46,Y,del(X)(p22.33)mat, dup(4)(q34.3q35.2)dn. aCGH analysis on the DNA extracted from the umbilical cord revealed arr [GRCh37 (hg19)] 4q34.3q35.2 (181,149,823-188,191,938) × 3.0, arr Xp22.33 (470,485-2,985,006) × 0 with a 7.042-Mb duplication of 4q34.3-q35.2 and a 2.514-Mb deletion of Xp22.33.
Conclusion:
A male fetus with del(X)(p22.33) and dup(4)(q34.3q35.2) may present congenital heart defects and short long bones on prenatal ultrasound.
Introduction:
Pure duplication of chromosome 18p is rare, with clinical phenotypes ranging from normal or slight abnormalities to various degrees of mental retardation. It remains difficult to establish a clear genotype-phenotype correlation.
Methods:
Chromosomal karyotyping analysis was performed on cultured amniotic fluid cells from three cases. Single nucleotide polymorphism (SNP) array analysis was carried out using the Illumina Human CytoSNP-12 BeadChip. We also carried out a review of the literature regarding 18p11 microduplication.
Results:
G-banding analysis showed that the three cases had normal karyotypes. SNP array results showed 0.48-1.6 Mb microduplications of 18p11.31-p11.22 (chr18: 6995739-8713088) in these cases, encompassing different degrees of LAMA1 duplication. Follow-up analysis showed that the parents of both cases 1 and 2 chose termination of pregnancy. Case 3 presented with normal growth and physical development. Currently, there is not enough evidence supporting the pathogenicity of LAMA1 triplosensitivity.
Conclusion:
We described three prenatal cases with 18p11.31-p11.22 microduplications involving part of the LAMA1 locus. There might be phenotypic diversity associated with 18p11.31-p11.22 microduplications. To avoid unnecessary abortions for pregnancies such as these, comprehensive genetic counseling should be offered.
