Molecular Cytogenetics最新文献

Partial trisomy 9p is one of the most frequent autosome anomalies in newborn infants featured by craniofacial dysmorphism, intellectual disability and psychomotor growth. Female patients carrying monosomy Xq usually show mild symptoms due to skewed X-chromosome inactivation (XCI). Unbalanced translocation between chromosome X and chromosome 9 is rare in prenatal diagnosis. The skewed inactivation of abnormal X would spread into the extra segment of chromosome 9 presented in the der(X) leading to mild phenotypes. We reported on a fetus with high risk of trisomy 9p(13.32 Mb 9p23-p24.3 duplication)suggested by noninvasive prenatal testing (NIPT), the fetus was normal by ultrasonography. G-banding with trypsin-giemsa (GTG), copy number variations sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were carried out to delineate the nature of rearrangement. Final karyotype of the fetus was identified as 46,X,der(X)t(X;9)(q27;p23)dn. An unbalanced X-autosome translocation with a deletion of Xqter-q27.2 and a duplication of 9pter-p23 led to mild phenotypes with no obvious alteration by prenatal ultrasonography, or obvious pathological alterations after pregnancy termination.

Background: Small supernumerary marker chromosomes (sSMC) are additional centric chromosome fragments too small to be identified by banding cytogenetics alone. A sSMC can originate from any chromosome and it is estimated that 70% of sSMC are de novo, while 30% are inherited. Cases of sSMC derived from chromosome 5 (sSMC5) are rare, accounting for1.4% of all reported sSMC cases. In these patients, the most common reported features are macrocephaly, dysmorphic facial features, heart defects, growth retardation, hypotonia, and intellectual disability. Also sSMC derived from chromosome 8 are very rare and the phenotype of patients with sSMC8 is very variable. Common clinical features of the patients include developmental delay, mental retardation, intellectual disability, hypotonia, hypospadias, attention deficit hyperactivity disorders (ADHD), skeletal anomalies, dysmorphic facial features, and renal dysplasia. To the best of our knowledge, in literature there are no cases with coexistence of sSMC5 and sSMC8, so we reviewed the literature to compare cases with SMC5 and those with SMC8 separately. This study is aimed to highlight the unique findings of a patient with the coexistence of sSMC5 and sSMC8.

Case presentation: We describe a female patient with two supernumerary markers derived from chromosome 5 (SMC5) and chromosome 8 (SMC8). The patient was born prematurely at 30 weeks with respiratory distress and bronchodysplasia. On physical examination she presented dysmorphic features, respiratory issues, congenital heart defect, developmental delay, and intellectual disability. The G-banded chromosome analysis on cultured lymphocytes revealed in all the analyzed cells a female karyotype with the presence of two supernumerary chromosomal markers and the array-CGH highlighted the region and the size of these two duplications. We also used the fluorescent in situ hybridization analysis (FISH) using painting of chromosomes 5 and 8 to confirm the origin of the two sSMC. So, the karyotype of the patient was: 48, XX, +mar1, +mar2.

Conclusions: This is the first case with two markers: one from chromosome 5 and one from chromosome 8. Based on the data reported, we can affirm that the phenotype of our patient is probably caused mainly by the presence of the sSMC.

Background: Copy number variants (CNVs) are an important source of normal and pathogenic genome variations. Especially CNVs identified in prenatal cases need careful considerations and correct interpretation if those are harmless or harmful variants from the norm.

Case presentation: Herein, we reported a paternally inherited duplication of 7.6 Mb in 7q31.3 with, surprisingly, a favorable outcome. GTG-banding and CMA on the DNA derived from uncultured amniocytes revealed a karyotype: 46,XX.arr[GRCh37] 7q31.31q31.33(118,601,001_126,177,044) × 3. Ultrasound examination showed no dysmorphisms or intrauterine growth restriction in the fetus and the father was clinically normal as well.

Conclusion: Prenatal detection of a 7.6 Mb in 7q31.31 to 7q31.33 duplication in a female fetus turned out to be a yet unreported unbalanced chromosome abnormality. This is another example that parental testing and GTG-banding are necessary additional tests to be done in prenatal cases, before a reliable conclusion on the meaning of an aberration can be drawn.

Background: Chromosomal imbalances of several megabasepair in size are normally deleterious for the carrier. Still, rarely reported are so-called "unbalanced chromosome abnormalities" (UBCAs), which are either gains or losses or equally large genomic regions, but the affected person is not or only minimally clinically affected. The knowledge of such UBCAs is imperative also in chromosomal microarray analysis (CMA) or noninvasive prenatal testing (NIPT).

Case presentation: A maternally inherited del(18)(p11.32p11.31) was identified in a over two generations in a Chinese family with normal phenotype. The affected region encompasses 19 genes, among which TGIF1 is expressed in fetal and adult nervous system. TGIF1 deletions and /or mutations have been seen in cases with holoprosencephaly but also non-affected individuals, suggesting incomplete penetrance and variable expressivity.

Conclusions: Deletions in the terminal region of chromosome 18 short arm have been reported previously in clinically healthy persons. Here a further family with an UBCA in 18p11.3 is added to the literature, suggesting a careful genetic counselling in comparable, especially prenatal cases.