Chromosomal deletion syndromes result from deletion of chromosome segments. Specific syndromes are characterized by their size and location, as well as any associated phenotypic abnormalities. Deletion in excess of 2% of original DNA mass usually results in death/abortion of the zygote. Large deletions (~5 Mb) not resulting in death tend to result in Chromosomal deletion syndromes. Deletions of this magnitude are visible using karyotyping techniques. Smaller deletions result in Microdeletion syndrome, which are detected using fluorescence in situ hybridization (FISH).
Chromosomal deletion syndromes include 4p-Deletion (Wolf-Hirschhorn syndrome), 5p-Deletion (Cri du chat syndrome), Prader-Willi syndrome, Angelman syndrome, and Jacobsen syndrome.
Development of these syndromes usually involve errors during chromosomal crossover that lead to the break off of large segments of DNA. Deletions can be proximal (i.e. closer to the centromere) or interstitial (several small deletions separated by short sequences of DNA), but are predominantly distal (i.e. terminal). Chromosome end segments are deleted during distal chromosomal deletions.
List of syndromes
edit| Disorder name | Chromosome | Chromosome size (Mb) | Deletion size (Mb) | % chromosome loss |
|---|---|---|---|---|
| 1p36 deletion syndrome | 1p36 | 247 | 1.5-10 | 0.6-4 |
| Wolf-Hirschhorn syndrome | 4p | 191 | 1.4-8.4 | 0.7-4.4 |
| Cri du chat syndrome | 5p | 181 | 10.5 | 5.8 |
| Jacobsen syndrome | 11q | 134 | 4.1-12.8 | 3.1-10 |
| Prader-Willi syndrome | 15q | 100 | 5-6 | 5-6 |
| Angelman syndrome | 15q | 100 | 3.5 | 3.5 |
| 18p deletion syndrome | 18p | 76 | 3.8-30 | 5-40 |
1p36 deletion syndrome
edit1p36 deletion syndrome occurs in individuals with haploinsufficiency of several genes. Deletions can range in size from 1.5 Mb (microdeletion syndrome) to 10 Mb. Haploinsufficiencies occur as terminal deletions, interstitial deletions, derivative chromosomes, and other complex rearrangements. There is no common breakpoint between patients, however, there are common breakpoint cluster regions. De novo 1p36 terminal deletions more often arose from the maternally inherited chromosome.[6]
1p36 deletion syndrome is characterized by abnormal craniofacial features and developmental delays. Other symptom that have been displayed by individuals include hypotonia, seizures, structural brain abnormalities, congenital heart defects, vision problems, hearing loss, skeletal anomalies, abnormalities of the external genitalia, and renal abnormalities.[7] The majority of individuals will only display a few of these symptoms.
Wolf-Hirschhorn syndrome
editWolf-Hirschhorn syndrome (WHS) consists of a deletion of the short arm of chromosome 4, distal to the 4p15.1-p15.2 bands[8]. This region represents approximately half of the p arm. The syndrome is also associated with microdeletions; deletions can range in size from 1.4 Mb to 8.4 Mb[9]. The proximal boundary of the WHS critical region (WHSCR) was defined by a 1.9 megabase terminal deletion of 4p16.3. Deletion of this loci result in a loss of an allele containing proposed candidate gene LEMT1, which is involved in Ca2+ signaling.[10]
Cri du chat syndrome
editCri du chat syndrome (also known as cat cry syndrome) consists of a terminal or interstitial deletion of the distal portion of the short arm of chromosome 5. Terminal deletions are usually characterized by the loss of a 10.5 Mb region of the 5p chromosome[11]. Interstitial deletions can consist of several separate deletions as small as 1.5 Mb each[11]. Variability among individuals may be attributed to the differences in breakpoints and/or their genotypes. Cri du chat syndrome is one of the most common contiguous gene deletion disorders with an incidence rate of 1 in 15,000 to 1 in 50,000 live births. Deletions are mainly de novo, inherited; arising from chromosome breakage during gamete formation in the father.
Phenotypical dysmorphic features of the face and neck are used for clinical evaluations. No specific correlation is found between size of deletion and severity of clinical features; results vary widely.[12]
Jacobsen syndrome
editPrader-Willi syndrome
editPrader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by a long arm deletion of chromosome 15. The deletions are typically 5-6 Mb in size[13]. PWS consists of severe infantile hypotonia with poor suck and failure to thrive; hypogonadism causing genital hypoplasia and pubertal insufficiency; characteristic facial features; early-childhood onset obesity and hyperphagia; developmental delay/mild intellectual disability; short stature; and a distinctive behavioral phenotype. Sleep abnormalities and scoliosis are common. Insufficiency of Growth hormone is common, and hormone replacement therapy provides improvement in growth, body composition, and physical attributes.[13]
Angelman syndrome
editAngelman syndrome is a neurodevelopmental disorder characterized by by a long arm deletion of chromosome 15. The deletions are typically 3.5 Mb in size[14]. AS is a clinically distinct disorder in which patients suffer from mental retardation, movement or balance disorder, typical abnormal behaviors, and severe limitations in speech and language. Most cases are caused by absence of a maternal contribution to the imprinted region on chromosome 15q11-q13[14].
18p deletion syndrome
editReferences
edit- ^ Heilstedt, Heidi A.; Ballif, Blake C.; Howard, Leslie A.; Lewis, Richard A.; Stal, Samuel; Kashork, Catherine D.; Bacino, Carlos A.; Shapira, Stuart K.; Shaffer, Lisa G. (2003-01-05). "Physical Map of 1p36, Placement of Breakpoints in Monosomy 1p36, and Clinical Characterization of the Syndrome". The American Journal of Human Genetics. 72 (5): 1200–1212. doi:10.1086/375179. ISSN 0002-9297. PMC 1180272. PMID 12687501.
- ^ Wieland, Ilse; Schanze, Denny; Schanze, Ina; Volleth, Marianne; Muschke, Petra; Zenker, Martin (2014-12-01). "A cryptic unbalanced translocation der(4)t(4;17)(p16.1;q25.3) identifies Wittwer syndrome as a variant of Wolf-Hirschhorn syndrome". American Journal of Medical Genetics Part A. 164 (12): 3213–3214. doi:10.1002/ajmg.a.36765. ISSN 1552-4833.
- ^ Fang, J-S; Lee, K-F; Huang, C-T; Syu, C-L; Yang, K-J; Wang, L-H; Liao, D-L; Chen, C-H (2008-06-01). "Cytogenetic and molecular characterization of a three-generation family with chromosome 5p terminal deletion". Clinical Genetics. 73 (6): 585–590. doi:10.1111/j.1399-0004.2008.00995.x. ISSN 1399-0004.
- ^ Cassidy, Suzanne B.; Schwartz, Stuart; Miller, Jennifer L.; Driscoll, Daniel J. (2012-01-01). "Prader-Willi syndrome". Genetics in Medicine. 14 (1): 10–26. doi:10.1038/gim.0b013e31822bead0. ISSN 1098-3600.
- ^ Smith, A.; Wiles, C.; Haan, E.; McGill, J.; Wallace, G.; Dixon, J.; Selby, R.; Colley, A.; Marks, R. (1996-02-01). "Clinical features in 27 patients with Angelman syndrome resulting from DNA deletion". Journal of Medical Genetics. 33 (2): 107–112. doi:10.1136/jmg.33.2.107. ISSN 1468-6244. PMID 8929945.
- ^ Heilstedt, Heidi A.; Ballif, Blake C.; Howard, Leslie A.; Lewis, Richard A.; Stal, Samuel; Kashork, Catherine D.; Bacino, Carlos A.; Shapira, Stuart K.; Shaffer, Lisa G. (2003-05-01). "Physical Map of 1p36, Placement of Breakpoints in Monosomy 1p36, and Clinical Characterization of the Syndrome". The American Journal of Human Genetics. 72 (5): 1200–1212. doi:10.1086/375179. PMC 1180272. PMID 12687501.
- ^ Battaglia, Agatino (1993-01-01). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora JH; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C. (eds.). 1p36 Deletion Syndrome. Seattle (WA): University of Washington, Seattle. PMID 20301370.
- ^ Battaglia, Agatino; Carey, John C.; South, Sarah T. (2015-09-01). "Wolf-Hirschhorn syndrome: A review and update". American Journal of Medical Genetics. Part C, Seminars in Medical Genetics. 169 (3): 216–223. doi:10.1002/ajmg.c.31449. ISSN 1552-4876. PMID 26239400.
- ^ Wieland, Ilse; Schanze, Denny; Schanze, Ina; Volleth, Marianne; Muschke, Petra; Zenker, Martin (2014-12-01). "A cryptic unbalanced translocation der(4)t(4;17)(p16.1;q25.3) identifies Wittwer syndrome as a variant of Wolf-Hirschhorn syndrome". American Journal of Medical Genetics Part A. 164 (12): 3213–3214. doi:10.1002/ajmg.a.36765. ISSN 1552-4833.
- ^ Zollino, Marcella; Lecce, Rosetta; Fischetto, Rita; Murdolo, Marina; Faravelli, Francesca; Selicorni, Angelo; Buttè, Cinzia; Memo, Luigi; Capovilla, Giuseppe (2003-03-01). "Mapping the Wolf-Hirschhorn Syndrome Phenotype Outside the Currently Accepted WHS Critical Region and Defining a New Critical Region, WHSCR-2". The American Journal of Human Genetics. 72 (3): 590–597. doi:10.1086/367925. PMC 1180235. PMID 12563561.
- ^ a b Fang, J.-S.; Lee, K.-F.; Huang, C.-T.; Syu, C.-L.; Yang, K.-J.; Wang, L.-H.; Liao, D.-L.; Chen, C.-H. (2008-06-01). "Cytogenetic and molecular characterization of a three-generation family with chromosome 5p terminal deletion". Clinical Genetics. 73 (6): 585–590. doi:10.1111/j.1399-0004.2008.00995.x. ISSN 1399-0004. PMID 18400035.
- ^ Nguyen, Joanne M.; Qualmann, Krista J.; Okashah, Rebecca; Reilly, AmySue; Alexeyev, Mikhail F.; Campbell, Dennis J. (2015-09-01). "5p deletions: Current knowledge and future directions". American Journal of Medical Genetics. Part C, Seminars in Medical Genetics. 169 (3): 224–238. doi:10.1002/ajmg.c.31444. ISSN 1552-4876. PMID 26235846.
- ^ a b Cassidy, Suzanne B.; Schwartz, Stuart; Miller, Jennifer L.; Driscoll, Daniel J. (2012-01-01). "Prader-Willi syndrome". Genetics in Medicine. 14 (1): 10–26. doi:10.1038/gim.0b013e31822bead0. ISSN 1098-3600.
- ^ a b Smith, A.; Wiles, C.; Haan, E.; McGill, J.; Wallace, G.; Dixon, J.; Selby, R.; Colley, A.; Marks, R. (1996-02-01). "Clinical features in 27 patients with Angelman syndrome resulting from DNA deletion". Journal of Medical Genetics. 33 (2): 107–112. doi:10.1136/jmg.33.2.107. ISSN 1468-6244. PMID 8929945.