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< Handbook of Genetic Counseling
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Ring Chromosome 22
Introduction and contracting
- May you clarify to me in your personal phrases why you had been referred to genetics?
- What’s your understanding of the chromosome outcomes?
- What are your essential questions or issues?
- Define session
- Clarify chromosome outcomes
- Take household historical past (ask normal questions i.e.) miscarriage, MR, studying disabilities, beginning defects, and so on.)
- Dr. will look at him and should ask extra questions on his medical historical past
- We are going to talk about what we all know and reply questions if we will
- Briefly clarify chromosomes and genes
- He has 46 chromosomes together with an X and Y which signifies what we already knew that he’s a boy
- He additionally has a part of an additional chromosome that has shaped a hoop
- The ring incorporates a part of chromosome 22 (present ideogram)
- a hoop normally varieties when the ends of a chromosome break off leaving “sticky ends” that then join.
- We do not actually know why rings type
- We additionally do not know the place the additional piece of chromosome initially got here from
- The presence of additional chromosomal materials can change the best way our our bodies develop and develop
- There aren’t any studies within the literature of people with an additional ring chromosome 22 that’s precisely just like the one present in _______.
- Subsequently it makes it tough to offer you a transparent thought of what to anticipate
- Particularly since there are two issues we’re contemplating, the additional genetic materials and the truth that it’s current in a hoop type
- Nevertheless, we will let you know about what we do know from studies within the literature which can be comparable in some methods
- I might like to handle your essential issues one of the best I can so please leap in with questions
Prospects with ring chromosomes
- Further ring chromosomes have been handed on from dad or mum to baby (a case of grandfather, father and son all with additional ring 22 that’s a lot small then _____’s ring)
- When the ring chromosome is copied earlier than cells divide generally there’s problem separating them and this may end up in the ring being altered (new break factors or duplication of a few of the materials)
- It’s thought that if they cannot separate the cell dies
- It tends to be extra frequent to have ring chromosomes current in a sure share of an individual’s cells and never all of them
- When that is the case the cells with the additional ring are thought to die (proof for this comes from the truth that generally when these people are retested there are not rings current or they’re present in a smaller share of cells.)
- Plainly _____ is doing higher than practically the entire people which were reported to have a duplication of all and even a part of chromosome 22 within the literature
- If people have a whole additional copy of chromosome 22 (that isn’t a hoop) they often die earlier than beginning or quickly after. Additionally they normally have a variety of beginning defects and attribute bodily options.
- People with partial deletions have been reported with a variety of bodily traits and well being issues that ______ doesn’t appear to have.
Phenotype seen in different instances
- Full trisomy 22 syndrome, der(22) syndrome, and cat eye syndrome (CES) all have some overlapping traits (see charts from articles describing traits with full and mosaic trisomy 22 and see chart itemizing options of CES)
- Usually related to supernumerary bisatellited marker chromosome (inv dup 22pter-22q11.2) leading to four copies of that area
- Extremely variable phenotype (identical marker leads to completely different phenotype in numerous generations)
- three copies have been sufficient to lead to CES phenotype (Reiss et al. 1985 and Knoll et al. 1994)
- Standards for prognosis of CES embrace;
- Ocular coloboma of the iris and or retina
- Anal atresia (with or with out fistula)
- Preauricular pores and skin tags and pits
- Coronary heart defects (particularly complete anomalous pulmonary venous return
- Dysmorphic options (hypertelorism, down-slanting palpegral fissures, urogenital defects, gentle to moderater MR
Minute supernumerary ring chromosome 22 related to CES
- three generations had the minute ring derived from 22q11.2
- ring current in 90% of blood cells over the three generations
- particular person affected with CES has four copies of this area in every cell (unaffected father and grandfather have three copies)
- father and paternal grandfather had no scientific options
- might have been spinoff of a dicentric marker chromosome
Case of duplication of 22q11.2-q13.1 and pericentric inversion (Prasher VP et al. 1995)
- Restricted communication abilities
- Persistent self damage
- Poor mobility
- Colobomata (frequent in cat eye syndrome)
- Distinguished brow
- Low posterior hairline
- Prognathism of decrease jaw
- Tongue protrusion
- Poor imaginative and prescient
- Wanted assist with day by day dwelling abilities
- Brief fingers and fingers
- Reasonable thoracic kyphosis
- Small penis and testes
- Bilateral single transverse palmar crease
- Absence of speech
- Persistent self-injury
- Lack of day by day dwelling abilities
- very poor imaginative and prescient
Case of de novo direct duplication of 22q11-q12
- Milder phenotype than full trisomy 22 and der(22)t(11:22)
- Comparable in sort and severity of cat eye syndrome (CES)
Different case of 22q11.2-q13.1 de novo duplication
- Minor bodily anomalies
- Bilateral preauricular pits
- Failure to thrive
- Extremely arched palate
- Bilateral hydronephrosis
- Delayed gross motor abilities
Mechanisms of ring formation
- By two DNA breaks, one in every arm of the identical chromosome, adopted by fusion of the proximal damaged ends. The causes of those DNA breaks are normally unknown and so is the mechanism behind ligation of the ends. It’s potential that the non-homologous end-joining equipment performs a job on this course of (Smith et al. 2001). A hoop will also be shaped by fusion at two breakpoints in the identical chromosome arm. Nevertheless, solely few examples of such rings have been described. Most likely, it’s because they’re acentric and can lack attachment level for the cell division equipment. Except there’s a completely different anchorage sequence for the kinetochore advanced they are going to be misplaced in subsequent mitoses. Such ÒneocentromereÓ sequences have, nonetheless, been described in uncommon instances of constitutional (Slater et al. 1999) and bought (Gisselsson et al. 1999) ring chromosomes.
- By fusion of dysfunctional telomeres from the identical chromosome. A number of in vitro and animal fashions have proven that shortening of telomeric DNA repeats results in the detachment of protecting proteins from the chromosome ends (Counter et al. 1992). This renders the chromosome ends susceptible to recombination with DNA both from different chromosomes Ð resulting in formation of a dicentric Ð or with the opposite arm of the identical chromosome Ð resulting in formation of a hoop.
- Dad and mom carrying acrocentric isochromosomes or homologous Robertsonian translocations have been identified to have youngsters with a hoop chromosome apparently derived from the parental abnormality (Mears AJ cites de Almeida et al. 1983 and Neri et al. 1983)
- Extranumerary can type when a marker chromosome breaks and ends of the monocentric fragment fuse
Constitutional ring chromosomes
- 1/50,000 human fetuses (Jacobs et al. 1975)
- In most cases, these rings are shaped by breakpoints in each arms, adopted by fusion of the proximal ends into a hoop with lack of the distal materials.
- Such rings might thus lead to scientific options mimicking terminal deletion syndromes.
Supernumary ring chromosomes
- Alternatively, congenital ring chromosomes are supernumerary, i.e. they happen along with two regular homologues of the corresponding chromosome (Anderlid et al. 2001)
- uncommon attributable to:
- really are uncommon in prevalence
- supernumerary ring chromosomes typically regularly disappear in vivo and solely cells with regular karyotype are finally noticed (Michalski Ok et al. 1993 cited Hoo et al. 1980)
- not very many studies makes it tough to foretell prognosis or present empiric threat information
- supernumerary marker chromosomes are extra frequent than supernumerary rings occurring in 1 in 1,500 to 1 in 500 for a (Michalski Ok et al. 1993 extrapolated this from a number of research from 1984-1990)
- the results shall be just like partial trisomies or duplications
- Completely different traits relying on:
- which chromosome is concerned
- the place of breakpoints inside the chromosome.
- sufferers with additional rings don’t solely show various signs ensuing from deletions or duplications
- In a meta-study together with greater than two-hundred sufferers with congenital ring chromosomes it has been demonstrated that almost all of youngsters with rings present a failure to thrive past the extent anticipated from their chromosomal imbalances (Kosztolanyi 1987).
- prompt that that is because of the mitotic instability of rings, stopping somatic cells from proliferating usually.
- speculation is supported by the truth that progress failure is extra frequent amongst sufferers with giant ring chromosomes, than amongst these with small ones (Kosztolanyi 1987).
- That is in accordance with the BFB mannequin of ring chromosome dynamics.
- Statistically, giant rings will endure extra sister chromatid exchanges per cell cycle than small rings and would thus have a better propensity for breaking at anaphase.
- In a standard cell, this provokes a physiological DNA harm response resulting in both cell cycle arrest or apoptosis (Cohen-Jonathan et al. 1999).
- a cell inhabitants carrying a hoop chromosome would proliferate slower than a inhabitants with out rings; the inhabitants with rings can be much less match and be at a selective drawback.
- Apparently, ring chromosome loss or measurement discount just isn’t unusual in instances with congenital rings.
- Particularly, instances with small rings typically exhibit a subclone with out the ring chromosome and these sufferers are thus ring/monosomy mosaics (Gisselsson et al. 1999).
Ring chromosomes at cell division
- In distinction to linear chromosomes, rings might endure cell division in three alternative ways (McClintock 1938; Lejeune 1968). Which of those pathways a hoop chromosome will observe is determined by the variety of sister chromatid exchanges (SCE) that has occurred within the ring earlier than cell division:
- No SCE or a good variety of SCEs in the identical path will allow regular, symmetrical segregation of the chromatids.
- A good variety of SCEs in numerous instructions will result in the formation of interlocked rings.
- An odd variety of SCEs will result in transformation from two parallel chromatids into one steady ring, with the double measurement of the unique rings (Fig. 2).
- Anderlid BM, Sahl n S, Schoumans J, Holmberg E, Ahsgren I, Mortier G, Speleman F, Blennow E (2001) Detailed characterization of 12 supernumerary ring chromosomes utilizing micro-FISH and seek for uniparental disomy. Am J Med Genet 99: 223-33. Artandi SE, DePinho RA (2000) A crucial function for telomeres in suppressing and facilitating carcinogenesis. Curr Opin Genet Dev 10: 39-46 Medline
- Gisselsson D, H glund M, Mertens F, Johansson B, Dal Cin P, Van den Berghe H, Earnshaw WC, Mitelman F, Mandahl N (1999) The construction and dynamics of ring chromosomes in human neoplastic and non-neoplastic cells. Hum Genet 104: 315-325 Medline
- Jacobs PA, Frackiewicz A, Regulation P, Hilditch CJ, Morton NE (1975) The impact of structural aberrations of the chromosomes on reproductive health in man. II. Outcomes. Clin Genet 8: 169-178 Medline
- Kosztolanyi G (1987) Does “ring syndrome” exist? An evaluation of 207 case studies on sufferers with a hoop autosome. Hum Genet 75: 174-179 Medline
- Lejeune J (1968) De la duplication de constructions circulaires. Ann Genet 11: 71-77 Medline
- McClintock B (1938) The manufacturing of homozygous poor tissues with mutant traits by the use of the aberrant habits of ring-shaped chromosomes. Genetics 23: 215-376
- McClintock B (1940) The steadiness of damaged ends of chromosomes in Zea Mays. Genetics 26: 234-282
- Slater HR, Nouri S, Earle E, Lo AW, Hale LG, Choo KH (1999) Neocentromere formation in a secure ring 1p32-p36.1 chromosome. J Med Genet 36: 914-918 Medline
- Smith J, Smith Ok, M zard C (2001) Tying up Free Ends: Era and Restore of DNA Double-Strand Breaks. http://www.infobiogen.fr/companies/chromcancer/Deep/DoubleStrandBreaksID20008.html
- Gisselsson D, Ring chromosomes: vicious circles on the finish and starting of life. Atlas Genet Cytogenet Oncol Haematol December 2001.
- URL : http://www.infobiogen.fr/companies/chromcancer/Deep/RingChromosID20030.html
The knowledge on this define was final up to date in July 2002.