Velo-cario-Facial Syndrome
Merlin G. Butler, F. John Meaney in Genetics of Developmental Disabilities, 2019
The loss of DNA that causes VCFS is an interstitial deletion from the long arm of chromosome 22 that resides within a region of the genome that is highly susceptible to mutation. This region of chromosome 22 seems to be one of the most mutable regions in the entire human genome, thus accounting for the high rate of spontaneous mutation and the large number of nonfamilial cases. The mechanism for the deletion has been determined to occur during gametogenesis (34). The rearrangement happens as a result of a recombinant event in the first meiotic prophase (Prophase I) during synapsis. There is an unusual arrangement of chromosome 22 in the region that marks the normal breakpoint for the proximal end of the deletion and the region at the distal end. In both of these regions, there occurs a series of low copy repeats (LCRs) of DNA that are largely homologous (Fig. 4).
100 MCQs from Dr. David Browne and Colleagues
David Browne, Selena Morgan Pillay, Guy Molyneaux, Brenda Wright, Bangaru Raju, Ijaz Hussein, Mohamed Ali Ahmed, Michael Reilly in MCQs for the New MRCPsych Paper A, 2017
This patient has a diagnosis of DiGeorge syndrome (velocardiofacial syndrome). The popular acronym is CATCH 22. C - Cardiac defects, A - Abnormal facies, T - Thymic hypoplasia, C - Cleft palate and microdeletion of chromosome 22. Twenty-five to thirty per cent of all people with this syndrome develop schizophrenia and 0.5% of people with schizophrenia have microdeletions in this region. Microdeletion in this region results in the loss of about 50–80 genes. This results in reduction in the gene encoding COMT, which has been identified also on chromosome 22. COMT acts by degrading catecholamines and has a role in cortical dopamine metabolism. Therefore, in the presence a compromised or low-activity COMT psychosis may result in this syndrome. These patients also have an elevated risk of intellectual disability. (40, p 82, 41)
Genetics
Stephan Strobel, Lewis Spitz, Stephen D. Marks in Great Ormond Street Handbook of Paediatrics, 2019
This is a disorder principally affecting the derivatives of the first and second branchial arches. Its features include facial asymmetry, macrostomia with lateral oral clefting, cleft palate and microtia (Figs 15.42, 15.43). Preauricular ear tags and epibulbar dermoids of the eye are key features (Fig. 15.44). Microphthalmia and coloboma also occur. Common extracranial features include hemivertrebrae, fused vertebrae and structural cardiac and renal abnormalities. Hearing is often affected. Diagnosis: is based on clinical findings and eliminating other diagnoses.Inheritance: sporadic.Differential diagnosis: chromosome 22 abnormalities, particularly duplication and additional marker 22.Treatment/Management/Surveillance: management is best co-ordinated by a multi-disciplinary craniofacial team including craniofacial surgeons, speech therapists, audiologists and ophthalmologists.
Mosaic cat eye syndrome in a child with unilateral iris coloboma
Published in Ophthalmic Genetics, 2021
Cristina Hernández-Medrano, Alberto Hidalgo-Bravo, Cristina Villanueva-Mendoza, Teresa Bautista-Tirado, David Apam-Garduño
Cat eye syndrome (CES) is a chromosomal disorder with an incidence of 1 per 50,000–150,000 live newborns (1). The classic triad of iris coloboma, anorectal malformations, and auricular abnormalities is present in 40% of patients (2). CES has a variable clinical spectrum, from patients with minor dysmorphias to patients with severe malformations. Among the minor dysmorphias, a high forehead, downslanting palpebral fissures, epicanthus, and preauricular pits or tags have been documented (3). Other ocular malformations described are microphthalmia, cataract, strabismus, and Duane anomaly (2,4,5). In addition, congenital heart defects and renal and gastrointestinal malformations have been reported in severe cases. Although cognition is usually normal, 30% of patients have an intellectual deficit (6). The genetic basis of CES was described in 1965 by Schachenmann, who noted the presence of a supernumerary bi-satellited marker chromosome derived from chromosome 22 (7). The ultimate result is a trisomy or partial tetrasomy of chromosome 22, specifically of the region 22pter to 22q11.1. Despite an analysis of several patients, the establishment of a genotype-phenotype correlation has not been possible (2,3,8).
The successful strategy of comprehensive pre-implantation genetic testing for beta-thalassaemia–haemoglobin E disease and chromosome balance using karyomapping
Published in Journal of Obstetrics and Gynaecology, 2022
Sirivipa Piyamongkol, Suchada Mongkolchaipak, Pimlak Charoenkwan, Rungthiwa Sirapat, Wanwisa Suriya, Tawiwan Pantasri, Theera Tongsong, Wirawit Piyamongkol
Nine embryos from family B were subjected to PGT. Karyomapping results of family B (beta-thalassaemia (c.17A>T)-Hb E disease) revealed six Hb E trait embryos (B1, B3, B4, B5, B6 and B9) and three affected with beta-thalassaemia–Hb E disease (B2, B7 and B8) (Figure 3). Standard mutation analysis using multiplex F-PCR and mini-sequencing confirmed haplotyping results in all embryos (Tables 2 and 3). Polymorphic marker analysis revealed the absence of extraneous DNA contamination in all samples. Additionally, karyomapping demonstrated three embryos with chromosome imbalance, 45, XY,-21 (embryo B2, affected), 45, XY,-22 (embryo B5, Hb E trait) and 47, XX,+16 (embryo B6, Hb E trait) (Figure 3). The absence of chromosome 21 in embryo B2 and chromosome 22 in embryo B5 was maternal. The gain of chromosome 16 of embryo B6 was maternal. Therefore, four Hb E trait embryos (B1, B3, B4 and B9) were identified for potential transfer. One Hb E trait embryo (B4) was chosen for transfer and patient B gave birth to a normal baby boy. Prenatal testing confirmed PGT results (Table 3).
CDKN2A Depletion Causes Aneuploidy and Enhances Cell Proliferation in Non-Immortalized Normal Human Cells
Published in Cancer Investigation, 2018
Zofia Hélias-Rodzewicz, Nelson Lourenco, Mariama Bakari, Claude Capron, Jean-François Emile
The function of genes within these regions was analyzed in National Center for Biotechnology Information (NCBI) referenced articles and databases, and 30 genes within 24 regions were selected as being particularly relevant for further in vitro study (Table 1). Within these genes, we then selected four of them (CDCA8, CCNDBP1, TP53BP1, CDK2NA) for further analysis; however, this selection is not exhaustive. Each of these genes was deleted in at least 50% of the tumor samples and the aberrations targeted regions <1.6Mb. One additional gene, localized on chromosome 22, was also included: CHEK2. Chromosome 22 is one of the chromosomes, the most frequently lost in GIST, and CHEK2 has been suggested as a candidate gene for tumorigenesis of GIST (22). This gene is mutated, albeit at low frequencies, in various cancers (23, 24). However, in our study, despite the frequent loss of chromosome 22 (11/22 cases), we did not observe any small aberrations of the region mapping CHEK2.
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