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Battaglia A, Carey JC, South ST. 2015. Wolf–Hirschhorn syndrome: A review and update. Am J

Med Genet Part C Semin Med Genet 169C:216–223. http://www.ncbi.nlm.nih.gov/pubmed/26239400

The authors, researchers and professors at the University of Utah School of Medicine, use data from multiple other research facilities and professors to ascertain their historical reference on the effect of Wolf-Hirschhorn syndrome. They find that there is plenty of room for further development in the science of understanding WHS. The authors of this article are trying to provide genotype-specific anticipatory guidance and recommendations to families of individuals with a diagnosis of WHS. They have found that the chromosomal basis of WHS consists of a deletion of the most terminal portion of the short arm of chromosome 4. Early on in the history of the syndrome, the deleted segment of the reported individuals represented about one half of the p arm.
 * The chromosomal basis of WHS consists of a deletion of the most terminal portion of the short arm of chromosome 4. The deleted segment of reported individuals represent about one half of the p arm, occurring distal to the bands 4p15.1-p15.2.
 * Many reports are particularly striking in the appearance of the craniofacial structure (prominent forehead, hypertelorism, the wide bridge of the nose continuing to the forehead) which has led to the descriptive term “Greek warrior helmet appearance”.
 * The proximal boundary of the WHSCR was defined by a 1.9 megabase terminal deletion of 4p16.3 that includes the proposed candidate genes LEMT1 and WHSC1. This was identified by two individuals that exhibited all 4 components of the core WHS phenotype, which allowed scientists to trace the loci of the deleted genes.
 * There is wide evidence that the WHS core phenotype (growth delay, intellectual disability, seizures, and distinctive craniofacial features) is due to haploinsufficiency of several closely linked genes as opposed to a single gene. Related genes that impact variation include:
 * WHSC2 (also known as NELF-A) is involved in multiple aspects of mRNA processing and the cell cycle
 * SLBP, a gene encoding Stem Loop Binding Protein, resides telomeric to WHSC2, and plays a crucial role in regulating histone synthesis and availability during S phase
 * LETM1 has initially been proposed as a candidate gene for seizures; it functions in ion exchange with potential roles in cell signaling and energy production.
 * FGFRL1, encoding a putative fibroblast growth factor decoy receptor, has been implicated in the craniofacial phenotype and potentially other skeletal features, and short stature of WHS
 * CPLX1 has lately been suggested as a potential candidate gene for epilepsy in WHS
 * PIGG gene (Phosphotidilinositol glycan anchor biosynthesis, class G), involved in the biogenesis of GPI anchor proteins, has recently been implicated in the occurrence of seizures
 * WHSC1 spans a 90-kb genomic region, two-thirds of which maps in the telomeric end of the WHCR; WHSC1 may play a significant role in normal development. Its deletion likely contributes to the WHS phenotype. However, variation in severity and phenotype of WHS suggests possible roles for genes that lie proximally and distally to the WHSCR

Nguyen, J., Qualmann, K., Okashah, R., Reilly, A., Alexeyev, M., & Campbell, D. (2015). 5p

deletions: Current knowledge and future directions. ''Am. J. Med. Genet. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 169''(3), 224-238. doi:10.1002/ajmg.c.31444. Epub 2015 Aug 3

http://www.ncbi.nlm.nih.gov/pubmed/26235846

Researchers and professors with medical degrees that are intensely studying the effects of chromosome deletions – specifically 5p deletions, wrote this article. This information on 5p deletions were first recognized in 1963 by Lejeune et al. Interestingly, 5p deletions occur on a molecular basis and result in changes in the phenotype due to a partial or total deletion of the short arm of chromosome 5. A high-pitched cry, dysmorphic features, poor growth, and developmental delay characterize the most recognizable phenotype. This information is useful for the Wikipedia article because it will further explain the effects of 5p deletions and their effect on a human phenotype. Also, the article explains means with which future directions can explore potential targeted therapies for individuals with 5p.
 * With an incidence of 1 in 15,000 to 1 in 50,000 live births, it is suggested to be one of the most common contiguous gene deletion disorders.
 * 5p deletions, whether terminal or interstitial, occur at different breakpoints; the variability seen among individuals may be attributed to the differences in their genotypes.
 * Individuals that make up the population of those affected by 5p deletions comprise the 5p Minus Society, an online family support group in the United States
 * 5p deletions are most commonly de novo occurrences, which are paternal in origin in 80–90% of cases, possibly arising from chromosome breakage during gamete formation in males
 * There is no specific correlation found between size of deletion and severity of clinical features because the results vary so widely
 * Some examples of the possible dysmorphic features include: downslanting palpebral fissures, broad nasal bridge,microcephaly, low-set ears, preauricular tags, round facies, short neck, micrognathia, and dental malocclusionhypertelorism, epicanthal folds, downturned corners of the mouth,

Turpin, R., & Lejeune, J. (1969). Human afflictions and chromosomal aberrations. Oxford:

Pergamon Press.

http://bucknell.worldcat.org/oclc/896838392

Turpin etc. writes on the effects of chromosomal aberrations that include deletions and their affect on karyotypes and phenotypes. The extent that chromosomal development impacts phenotype can range, but includes a few types of isolated deletion without tanslocation that exhibits a dysmorphic syndrome that possibly notes the following signs: hypertelorism with incomplete convergence in the right eye, low set ears and deformed hands (high setting of the thumb and curving of the fifth finger) and feet (syndactyly of the third and fourth toes). The karyotype with 46 chromosomes revealed the absence of a chromosome 18 replaced by a telocentric the arm of which was identical in size to that of the long arm of 18. The most plausible explanation for such an anomaly is loss of the short arm of 18 just above the centromere. This is written for people with a basic knowledge of the impact of chromosomal properties. It is useful to analyze the paper because of its relevance and it’s description of chromosomal actions.

Yang, X., Fu, F., Li, R., Zhang, Y., Wan, J., Yang, X.,. .. Liao, C. (2015). Application of

chromosome microarray analysis for fetuses with increased nuchal translucency and a normal karyotype. 32(3), 370-374. doi:10.3760/cma.j.issn.1003-9406.2015.03.015 http://www.ncbi.nlm.nih.gov/pubmed/26037353

The authors are from the Prenatal Diagnostic Center in the Women and Children's Medical Center of Guangzhou. The article describes that well-known micro deletion or microduplication syndromes including Wolf-Hirschhorn syndrome, 22q11 microdeletion syndrome and ATR-16 syndrome were identified. This furthers my acquisition of the article reviewing 4p syndrome. For fetuses with increased nuchal translucency, chromosome microarray analysis can identify chromosomal microdeletion/microduplication unrecognizable by conventional karyotyping analysis. This article can peer further into the many different deletory syndromes that occur chromosomally.

Zorlu, P., Eksioglu, A., Ozkan, M., Tos, T., & Senel, S. (2014). A rare subtelomeric deletion

syndrome: Wolf Hirschhorn syndrome. Genetic Counseling, 25 (3), 299-303. http://www.ncbi.nlm.nih.gov/pubmed/25365852

This article was written by professors and doctors in their field, and the article underwent peer-review in order to be published in the journal, Genetic Counseling. The authors of this article explain the effects of Wolf Hirschhorn syndrome. It is caused by a deletion of the distal portion of the short arm of chromosome 4. Often, it can be characterized by psychomotor retardation, seizures, and congenital malformations. Major complications are severe growth retardation, developmental delay, seizures, feeding difficulties due to hypotonia, and predisposition to respiratory infections. This article also provides sources for patient’s family to assist in counseling for the patient to progress in motor skills, speech, and social interaction.