Phenotypes and genotypes of the chromosomal instability syndromes.

As defined initially, chromosome instability syndromes (CIS) are a group of inherited conditions transmitted in autosomal recessive pattern characterised with both mental and physical development delay generally. They are also with other medical complications in individuals with CIS commonly including different degree of dysmorphics, organs/systems dys-function and high risk of cancer predisposition. Chromosomal breakage from CIS can be seen either in spontaneous breakage around 10-15% observed in Fanconi anemia or induced by clastogenic agents such as mitomycin (MMC), diepoxybutane (DEB).

Advances in genetic studies of inherited bone marrow failure syndromes and their associated malignancies.

The inherited bone marrow failure syndromes (IBMFS) are a rare group of heterogeneous genetic disorders characterised by bone marrow failure, commonly associated with one or more congenital anomalies found in patients which have a familiar predisposition. Genetic detection of IBMFS disease types is not only to benefit to affected patients but also of help to relatives unaffected phenotypically. Patients with IBMFS have a high risk of hematologic malignancies, commonly myelodyspastic syndrome (MDS), acute myeloid leukemia (AML) and specific types solid tumours.

Fanconi anemia pathway defects in inherited and sporadic cancers.

Fanconi anemia (FA) is a recessive chromosomal instability syndrome. It is a hereditary disorder with defects in DNA repair characterized by progressive bone marrow failure, variable congenital malformations and predisposition to develop hematological or solid tumors. Bi-allelic gene mutations in FA cause not only the FA phenotype but also genome instability and additional mutations in their somatic cells resulting in a high predisposition to many different types of cancers.

Advances in the medical research and clinical applications on the plasma DNA.

Plasma DNA has had a strong impact and influence on basic medical research and clinical practice since the discovery of low levels of plasma DNA in healthy individuals under different physiological conditions. Although the source of circulating DNA still requires further investigation, a wide range of research has also proven the value of qualitative and quantitative measurements of plasma DNA in many disease conditions. The use of plasma DNA has a biomarker is advantageous due to accessibility, reliability, reproducibility, sensitivity, specific and relatively low cost.

Spectral karyotyping: an unique technique for the detection of complex genomic rearrangements in leukemia.

Spectral karyotyping (SKY) is a novel cytogenetic technique, has been developed to unambiguously display and identify all 24 humans chromosomes at one time without a priori knowledge of any abnormalities involved. SKY can discern the aberrations that can't be detected very well by conventional banding technique and Fluorescent in situ hybridization (FISH). So SKY is hyper accurate, hypersensitive, and hyper intuitionist.

Genetics of hereditary neurological disorders in children.

Hereditary neurological disorders (HNDs) are relatively common in children compared to those occurring in adulthood. Recognising clinical manifestations of HNDs is important for the selection of genetic testing, genetic testing results interpretation, and genetic consultation. Meanwhile, advances in next generation sequencing (NGS) technologies have significantly enabled the discovery of genetic causes of HNDs and also challenge paediatricians on applying genetic investigation.

The concept and practice of Fanconi Anemia: from the clinical bedside to the laboratory bench.

Fanconi Anemia (FA) is characterised with multiple gene mutations, multiple types of genetic abnormalities, multiple organ involvements and multiple types of cancer risks. It is a life threatening disease commonly at 5 years old children. Research on FA is one of the fastest areas in medical research field.

Resolution of trisomic mosaicism in prenatal diagnosis: estimated performance of a 50K SNP microarray.

Objective: To evaluate the ability of a DNA single nucleotide polymorphism (SNP) microarray to detect chromosome mosaicism for trisomy in prenatal samples in order to compare this with conventional cytogenetics.

Method: We created a dilution series of mock mosaic samples, by mixing measured amounts of fibroblast cells containing trisomy 8 from a male with aliquots of cells with a normal female karyotype. DNAs were extracted from these mosaic mixtures, then analysed on the Affymetrix 50K Xba SNP chip.

Molecular distinction between true centric fission and pericentric duplication-fission.

Centromere (centric) fission, also known as transverse or lateral centric misdivision, has been defined as the splitting of one functional centromere of a metacentric or submetacentric chromosome to produce two derivative centric chromosomes. It has been observed in a range of organisms and has been ascribed an important role in karyotype evolution; however, the underlying mechanisms remain unknown. We have investigated four cases of apparent centric fission in humans.

Issues arising from the prenatal diagnosis of some rare trisomy mosaics--the importance of cryptic fetal mosaicism.

Objectives: To add to the knowledge of fetal mosaicism, confined placental mosaicism (CPM), and uniparental disomy (UPD), in rare trisomies detected at prenatal diagnosis.

Methods: The origin of rare trisomy mosaics, mostly (8/11) seen in amniocytes, was examined in 11 cases by follow-up karyotyping and the study of microsatellite inheritance.

Results: Of the rare trisomies presented, three were mosaic trisomy 16 (two of which were CPM), and the remainder comprised single cases of mosaic trisomies of 8, 9, 10, 11, 12, 14, 5 and 15--the last two being CPM.

Three different origins for apparent triploid/diploid mosaics.

Four apparent triploid/diploid mosaic cases were studied. Three of the cases were detected at prenatal diagnosis and the other was of an intellectually handicapped, dysmorphic boy. Karyotypes were performed in multiple tissues if possible, and the inheritance of microsatellites was studied with DNA from fetal tissues and parental blood.

Chromosome 13q neocentromeres: molecular cytogenetic characterization of three additional cases and clinical spectrum.

We report three new cases of chromosome 13 derived marker chromosomes, found in unrelated patients with dysmorphisms and/or developmental delay. Molecular cytogenetic analysis was performed using fluorescence in situ hybridization (FISH) with chromosome-specific painting probes, alpha satellite probes, and physically mapped probes from chromosome 13q, as well as comparative genomic hybridization (CGH). This analysis demonstrated that these markers consisted of inversion duplications of distal portions of chromosome 13q that have separated from the endogenous chromosome 13 centromere and contain no detectable alpha satellite DNA.