First-Tier Array CGH in Clinically Variable Entity Diagnosis: 22q13.3 Deletion Syndrome

Phelan-McDermid (PMS) or 22q13 deletion syndrome (OMIM 606232) is a rare genetic disorder with highly variable clinical presentation. The phenotype includes generalized neonatal hypotonia, developmental delay with intellectual disability and delayed speech, mild dysmorphic features, and autistic behavior. The genetic defects of PMS consist of 22q13.3 deletions or chromosomal structural rearrangements involving SHANK3 gene; the loss of function mutations of SHANK3 gene was reported in a minority of cases. The 22q13.3 deletions vary in size, from 0.2 to over 9 Mb, and, although larger deletions are generally associated with more severe phenotypes, the genotype-phenotype correlations are not clear-cut for all patients. SHANK3 is considered the main candidate gene for the neurologic features of PMS. PMS is a rare disorder, often underdiagnosed. There are no established clinical diagnostic criteria for PMS. The genetic tests typically used are chromosomal microarray and multiplex ligation-dependent probe amplification (MLPA) or fluorescent in situ hybridization (FISH) for copy number analysis of SHANK3 gene; next-generation sequencing (NGS) or Sanger sequencing is used for pathogenic mutation screening of SHANK3. In this chapter, we report three cases with PMS and summarize the clinical and genetic diagnostic approaches of this condition, highlighting the role of chromosomal microarray technology in the identification of rare, but significantly impacting patient’s life, DNA copy number abnormalities.

The Energy as a Determinant Factor in the Ethiopathogeny of Chromosomal Abnormalities. The Unsuspected Bioenergetic Role of Melanin

In the study of chromosomal abnormalities, in genetics, and in medicine in general, attention is rarely paid to the role of energy in the healthy subject and in the sick patient. The research on the chromosomal anomalies that are constantly published, does not mention the energy necessary for the biochemical processes involved in the function, replication and formation of genes, to be carried out in an adequate way. It seems that it is assumed that energy levels are always fine or at least did not have a significant role in the conditions associated with what we call chromosomal anomalies. A characteristic of the cell nucleus that has gone unnoticed is that it contains neither mitochondria nor ATP, much less glucose. Perhaps because of this, some researchers and clinicians come to think that the nucleus of cells does not require energy. The purpose of this work is to draw attention to the importance of energy levels in all the metabolic processes of the cell; and to make known that glucose is not an energy source, as it is only a source of carbon chains; and finally remark that our body, through melanin, can take energy directly from light.

Gene Polymorphisms That Predispose Women for Down Syndrome Child Birth

Down syndrome caused by presence of extra chromosome 21 originates from nondisjunction during parental gametogenesis. For overwhelming cases, the error occurs in oocyte and all the nondisjunction events are not stochastic. With increasing number of research efforts, it has come to know that maternal genetic architecture may be considered as risk factors for chromosomal errors. Polymorphisms of the genes involved in chromosome segregation, recombination and folic acid metabolisms have been investigated for their association with Down syndrome child birth. But the results are conflicting owing to ethnic and sociocultural differences. Here, we have discussed and summarized the outcome of the studies conducted on different population sample from different parts of world and tried to figure out the common polymorphisms, which could be used as makers for preconceptional screening of Down syndrome child birth risk among the women.

Current Cytogenetic Abnormalities in Acute Myeloid Leukemia

Cytogenetic abnormalities are frequently reported in the literature describing the presence of chromosomal rearrangements in important cases of acute myeloid leukemia (AML); the rate can reach 50–60% of cases of AML. Cytogenetic abnormalities represent an important prognosis factor, their analysis is crucial for AML; cytogenetic study permits to classify prognostic groups and indicate the treatment strategy and helps to improve the outcome of these patients and to increase their chances of cure. Hundreds of uncommon chromosomal aberrations from AML exist. This chapter summarizes chromosomal abnormalities that are common and classifies AML according to the World Health Organization (WHO) classifications from 2008 to 2016; we will discuss briefly gene mutations detected in normal karyotype (NK) AML by cutting-edge next-generation sequencing technology, like FLT3-ITD, nucleophosmin (NPM1), CCAAT/enhancer-binding protein alpha (CEBPA), and other additional mutations.

Impact of Biological Factors Related to Maternal Aging: Risk of Childbirth with Down Syndrome

Maternal aging and different biological factors play an important role in the birth of Down syndrome baby. Hormones play a crucial role for the maintenance of female sex cycle and oocyte maturation. Disparity in the level of these hormones during menstrual cycle has profound effect on female reproductive system. Hormonal imbalance also affects meiotic process and integrity of spindle structure and leads to nondisjunction of chromosome. Follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH) and luteinizing hormone (LH) play a crucial role in ovarian aging and nondisjunction of chromosomes. FSH stands as a hormonal indicator for ovarian aging, and its high level is responsible for aneuploid birth. Advanced chronological age of mother, ovarian aging, environmental factors and accelerated telomere shortening at older reproductive age are found to be risk factors for the birth of trisomy 21 Down syndrome.

Polyploidy in the Ginger Family from Thailand

Polyploidy is common in the ginger family Zingiberaceae. The aims of the present paper are (1) to provide a general introduction on species diversity with emphasis on conservation; (2) to highlight the human-use significance of this family, focusing on the two major genera, Zingiber (ginger) and Curcuma (turmeric); (3) to present chromosome number data from 45 natural and cultivated Curcuma taxa from Thailand, of which polyploids are predominant; and (4) to describe our own work on cytotaxonomy of selected Thai Curcuma species. We obtained somatic chromosome numbers from root tips and analysed meiotic chromosome behaviour from flowers. We also used the molecular cytogenetic method of ribosomal gene mapping on chromosomes to infer mechanism of polyploidization and reveal genomic relationships among closely related species. The main results of our cytogenetic studies include the following. The most sought-after medicinal Curcuma cultivars growing on a large-scale basis are secondary triploids, so as taxa in natural habitats that are harvested for local utilisation. These triploids are sexually deficient, due to meiotic pairing abnormalities, but they are propagated asexually via rhizomes. The ribosomal mapping results indicate natural triploidization process via hybridisation, either within populations or across the species boundaries.

The Risk of Chromosomal Abnormalities in Cases of Minor and Major Fetal Anomalies in the Second Trimester

Currently, noninvasive intrauterine screening for most chromosome abnormalities is available, but ultrasound examinations also play an important role during pregnancy, by drawing the attention to the suspect of a possible abnormality. Fetal ultrasound disorders can be classified into two major groups: (1) Major abnormalities are actually diagnosed malformations that are often associated with certain chromosome abnormalities but may be associated with other disorders (multiplex malformation) and may occur as isolated disorders (e.g., cardiac disorders, duodenal atresia, omphalocele, cystic hygroma (CH)). (2) Minor anomalies (“soft markers”) are not abnormal in themselves but are mild abnormalities that may occur in normal pregnancy but also increase the risk of certain chromosome aberrations. The minor anomalies in the second trimester include thickened nuchal fold (NF), mild ventriculomegaly, pyelectasis, hyperechogenic bowels, hyperechogenic papillary muscle, and shorter long bones. Plexus choroid cyst which is classified as a minor marker does not increase the risk of Down syndrome but increases the risk of trisomy 18 (Edwards syndrome). We want to emphasize the importance of screening of minor and major ultrasound abnormalities in detecting chromosomal abnormalities in the second trimester.

Maize Chromosome Abnormalities and Breakage-Fusion-Bridge Cycles in Callus Cultures

The maize karyotype was first characterized by the observation of pachytene chromosomes. The somatic chromosomes were identified by C-banding and FISH with repetitive DNA sequences. C-banding was useful for the identification of chromosome abnormalities in callus cultures. In the present review, we focus on the involvement of heterochromatic knobs on the occurrence of chromosome abnormalities in callus cultures. In a previous work we detected anaphase bridges resulting from delayed chromatid separation at knob regions and typical bridges derived from dicentric chromatids in cultures. The analysis of altered chromosomes showed they were derived from a chromatid-type breakage-fusion-bridge (BFB) cycle. Fluorescent in situ hybridization (FISH) showed signals of telomere sequences in the broken chromosome arm, thus giving evidence of de novo telomere formation on the broken chromosome end. Further observations of long- and short-term cultures have shown the presence of chromosome alterations derived from BFB cycles followed by chromosome healing. Additionally, the occurrence of unequal crossing over in a knob region was observed in callus culture. These results are of interest for studies on the mechanisms of chromosome alterations during evolution.