Poikiloderma with neutropenia

 

  • Arnold AW, Itin PH, Pigors M, Kohlhase J, Bruckner-Tuderman L, Has C. Poikiloderma with neutropenia: a novel C16orf57 mutation and clinical diagnostic criteria. Br J Dermatol. 2010 Oct;163(4):866-9. doi: 10.1111/j.1365-2133.2010.09929.x. Epub 2010 Sep 7.
  • Colombo EA, Bazan JF, Negri G, Gervasini C, Elcioglu NH, Yucelten D, Altunay I, Cetincelik U, Teti A, Del Fattore A, Luciani M, Sullivan SK, Yan AC, Volpi L, Larizza L. Novel C16orf57 mutations in patients with Poikiloderma with Neutropenia: bioinformatic analysis of the protein and predicted effects of all reported mutations. Orphanet J Rare Dis. 2012 Jan 23;7:7. doi: 10.1186/1750-1172-7-7.
  • Farruggia P, Indaco S, Dufour C, Lanza T, Mosa C, Macaluso A, Milioto M, D’Angelo P, Lanciotti M. Poikiloderma with neutropenia: a case report and review of the literature. J Pediatr Hematol Oncol. 2014 May;36(4):297-300. doi: 10.1097/MPH.0b013e31829f35e7. Review.
  • Hilcenko C, Simpson PJ, Finch AJ, Bowler FR, Churcher MJ, Jin L, Packman LC, Shlien A, Campbell P, Kirwan M, Dokal I, Warren AJ. Aberrant 3′ oligoadenylation of spliceosomal U6 small nuclear RNA in poikiloderma with neutropenia. Blood. 2013 Feb 7;121(6):1028-38. doi: 10.1182/blood-2012-10-461491. Epub 2012 Nov 27.
  • Koparir A, Gezdirici A, Koparir E, Ulucan H, Yilmaz M, Erdemir A, Yuksel A, Ozen M. Poikiloderma with neutropenia: genotype-ethnic origin correlation, expanding phenotype and literature review. Am J Med Genet A. 2014 Oct;164A(10):2535-40. doi: 10.1002/ajmg.a.36683. Epub 2014 Jul 16.
  • Mroczek S, Dziembowski A. U6 RNA biogenesis and disease association. Wiley Interdiscip Rev RNA. 2013 Sep-Oct;4(5):581-92. doi: 10.1002/wrna.1181. Epub 2013 Jun 14. Review.
  • Mroczek S, Krwawicz J, Kutner J, Lazniewski M, Kuciński I, Ginalski K, Dziembowski A. C16orf57, a gene mutated in poikiloderma with neutropenia, encodes a putative phosphodiesterase responsible for the U6 snRNA 3′ end modification. Genes Dev. 2012 Sep 1;26(17):1911-25. doi: 10.1101/gad.193169.112. Epub 2012 Aug 16.
  • Shchepachev V, Azzalin CM. The Mpn1 RNA exonuclease: cellular functions and implication in disease. FEBS Lett. 2013 Jun 27;587(13):1858-62. doi: 10.1016/j.febslet.2013.05.005. Epub 2013 May 15. Review.
  • Volpi L, Roversi G, Colombo EA, Leijsten N, Concolino D, Calabria A, Mencarelli MA, Fimiani M, Macciardi F, Pfundt R, Schoenmakers EF, Larizza L. Targeted next-generation sequencing appoints c16orf57 as clericuzio-type poikiloderma with neutropenia gene. Am J Hum Genet. 2010 Jan;86(1):72-6. doi: 10.1016/j.ajhg.2009.11.014. Epub 2009 Dec 10. Erratum in: Am J Hum Genet. 2010 Sep 10;87(3):445.
  • Walne AJ, Vulliamy T, Beswick R, Kirwan M, Dokal I. Mutations in C16orf57 and normal-length telomeres unify a subset of patients with dyskeratosis congenita, poikiloderma with neutropenia and Rothmund-Thomson syndrome. Hum Mol Genet. 2010 Nov 15;19(22):4453-61. doi: 10.1093/hmg/ddq371. Epub 2010 Sep 3.
  • Wang L, Clericuzio C, Larizza L. Poikiloderma with Neutropenia. 2017 Oct 26. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Available from http://www.ncbi.nlm.nih.gov/books/NBK459118/

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Fibromyalgia – Genetics Home Reference

 

Fibromyalgia is known to run in families, suggesting that genetic factors contribute to the risk of developing this disease. However, little is known for certain about the genetic basis of fibromyalgia. It is likely that variations in many genes, each with a small effect, combine to increase the risk of developing this condition.

The signs and symptoms of fibromyalgia are related to the way the brain recognizes and interprets pain signals. People with fibromyalgia have an increased sensitivity to pain; they feel pain more acutely than others would in response to a given stimulus. Researchers describe this phenomenon as the “volume” of pain sensations being turned up too high (pain amplification). Studies of the genetics of fibromyalgia have focused on genes with roles in the way the brain processes pain. For example, several genes that may influence the condition are involved in the production and breakdown of certain chemical messengers called . These chemicals relay signals between nerve cells that can increase or decrease the sensation of pain, a process known as pain modulation.

Nongenetic (environmental) factors also play critical roles in a person’s risk of developing fibromyalgia. The disorder can be triggered by infection or illness that would not otherwise cause chronic pain, injury, and other physical stress. Psychological and social factors such as a history of childhood abuse or neglect, exposure to war or other catastrophic events, and low job or life satisfaction have also been associated with an increased risk of fibromyalgia. Additionally, physical inactivity, obesity, and sleep disturbances seem to increase risk. However, many people who develop this condition do not have any recognized triggers or risk factors. It is likely that environmental conditions interact with genetic factors to determine the overall risk of developing this disorder.

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Lyme disease – Genetics Home Reference

 

Lyme disease is an infectious disease caused by Borrelia burgdorferi bacteria. The bacteria are transferred to humans by tick bite, specifically by blacklegged ticks (commonly known as deer ticks). The condition is named for the location in which it was first described, the town of Lyme, Connecticut.

If not treated with antibiotics, Lyme disease follows three stages: early localized, early disseminated, and late disseminated infection. A small percentage of individuals have symptoms that persist months or years after treatment, which is called post-treatment Lyme disease syndrome.

A characteristic feature of Lyme disease, and the key feature of early localized infection, is a slowly expanding red rash on the skin (called erythema migrans) at the site of the tick bite; the rash is often bull’s-eye shaped. Flu-like symptoms and enlarged lymph nodes (lymphadenopathy) are also early signs of infection. Most people who are treated at this stage never develop further symptoms.

The early disseminated stage of Lyme disease occurs as the bacteria is carried throughout the body in the bloodstream. This stage occurs a few weeks after the tick bite. Signs and symptoms can include additional rashes on other parts of the body, flu-like symptoms, and lymphadenopathy. Some affected individuals develop neurologic problems (referred to as neuroborreliosis), such as paralyzed muscles in the face (facial palsy); pain, numbness, or weakness in the hands or feet; difficulty concentrating; or memory problems. Rarely, the heart is affected (Lyme carditis), causing a sensation of fluttering or pounding in the chest (palpitations) or an irregular heartbeat.

The late disseminated stage of Lyme disease can occur months to years after the tick bite. The most common feature of this stage, Lyme arthritis, is characterized by episodes of joint pain and swelling, usually affecting the knees. In rare cases, the late disseminated stage also involves neurological problems.

Individuals with post-treatment Lyme disease syndrome report ongoing exhaustion (fatigue), muscle and joint achiness, headache, or difficulty concentrating even after treatment with antibiotics, when there is no evidence of the bacteria in the body. Very rarely, individuals have joint pain and swelling for months or years after successful antibiotic treatment. This complication is called antibiotic-refractory Lyme arthritis.

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Spastic paraplegia type 49 – Genetics Home Reference

 

Spastic paraplegia type 49 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve only the lower limbs, whereas the complex types also involve the upper limbs (to a lesser degree) and other problems with the nervous system. Spastic paraplegia type 49 is a complex hereditary spastic paraplegia.

Spastic paraplegia type 49 often begins with weak muscle tone (hypotonia) that starts in infancy. During childhood, spasticity and paraplegia develop and gradually worsen, causing difficulty walking and frequent falls. In addition, affected individuals have moderate to severe intellectual disability and distinctive physical features, including short stature; chubbiness; an unusually small head size (); a wide, short skull (); a short, ; and . Some people with spastic paraplegia type 49 develop seizures.

Problems with autonomic nerve cells (autonomic ), which control involuntary body functions such as heart rate, digestion, and breathing, result in several features of spastic paraplegia type 49. Affected individuals have difficulty feeding beginning in infancy. They experience a backflow of stomach acids into the esophagus (called or GERD), causing vomiting. GERD can also lead to recurrent bacterial lung infections called aspiration pneumonia, which can be life-threatening. In addition, people with spastic paraplegia type 49 have problems regulating their breathing, resulting in pauses in breathing (apnea), initially while sleeping but eventually also while awake. Their blood pressure, pulse rate, and body temperature are also irregular.

People with spastic paraplegia type 49 can develop recurrent episodes of severe weakness, hypotonia, and abnormal breathing, which can be life threatening. By early adulthood, some affected individuals need a machine to help them breathe (mechanical ventilation).

Other signs and symptoms of spastic paraplegia type 49 reflect problems with sensory neurons, which transmit information about sensations such as pain, temperature, and touch to the brain. Many affected individuals are less able to feel pain or temperature sensations than individuals in the general population. Affected individuals also have abnormal or absent reflexes (areflexia).

Because of the nervous system abnormalities that occur in spastic paraplegia type 49, it has been suggested that the condition also be classified as a hereditary sensory and autonomic neuropathy, which is a group of conditions that affect sensory and autonomic neurons.

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Microcephaly, seizures, and developmental delay – Genetics Home Reference

 

  • Dumitrache LC, McKinnon PJ. Polynucleotide kinase-phosphatase (PNKP) mutations and neurologic disease. Mech Ageing Dev. 2017 Jan;161(Pt A):121-129. doi: 10.1016/j.mad.2016.04.009. Epub 2016 Apr 26. Review.
  • Poulton C, Oegema R, Heijsman D, Hoogeboom J, Schot R, Stroink H, Willemsen MA, Verheijen FW, van de Spek P, Kremer A, Mancini GM. Progressive cerebellar atrophy and polyneuropathy: expanding the spectrum of PNKP mutations. Neurogenetics. 2013 Feb;14(1):43-51. doi: 10.1007/s10048-012-0351-8. Epub 2012 Dec 9.
  • Reynolds JJ, Walker AK, Gilmore EC, Walsh CA, Caldecott KW. Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair. Nucleic Acids Res. 2012 Aug;40(14):6608-19. doi: 10.1093/nar/gks318. Epub 2012 Apr 15.
  • Shen J, Gilmore EC, Marshall CA, Haddadin M, Reynolds JJ, Eyaid W, Bodell A, Barry B, Gleason D, Allen K, Ganesh VS, Chang BS, Grix A, Hill RS, Topcu M, Caldecott KW, Barkovich AJ, Walsh CA. Mutations in PNKP cause microcephaly, seizures and defects in DNA repair. Nat Genet. 2010 Mar;42(3):245-9. doi: 10.1038/ng.526. Epub 2010 Jan 31.
  • Shimada M, Dumitrache LC, Russell HR, McKinnon PJ. Polynucleotide kinase-phosphatase enables neurogenesis via multiple DNA repair pathways to maintain genome stability. EMBO J. 2015 Oct 1;34(19):2465-80. doi: 10.15252/embj.201591363. Epub 2015 Aug 19.
  • Weinfeld M, Mani RS, Abdou I, Aceytuno RD, Glover JN. Tidying up loose ends: the role of polynucleotide kinase/phosphatase in DNA strand break repair. Trends Biochem Sci. 2011 May;36(5):262-71. doi: 10.1016/j.tibs.2011.01.006. Epub 2011 Feb 25. Review.

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Alopecia areata – Genetics Home Reference

 

The causes of alopecia areata are complex and not well understood. A combination of factors likely underlies the disorder, including changes in many genes that function in the hair and skin and in the immune system.

Alopecia areata is one of a large group of immune system diseases classified as autoimmune disorders. Normally, the immune system protects the body from foreign invaders, such as bacteria and viruses, by recognizing and attacking these invaders and clearing them from the body. In autoimmune disorders, the immune system malfunctions and attacks the body’s own tissues instead. For reasons that are unclear, in alopecia areata the immune system targets , stopping hair growth. However, the condition does not permanently damage the follicles, which is why hair may later regrow.

Many of the genes that have been associated with alopecia areata participate in the body’s immune response. These include several genes belonging to a gene family called the . The HLA complex helps the immune system distinguish the body’s own proteins from proteins made by foreign invaders. Each HLA gene has many different variations, allowing each person’s immune system to react to a wide range of foreign proteins. Certain variations in HLA genes likely contribute to the inappropriate immune response targeting hair follicles that leads to alopecia areata. Immune system genes outside the HLA complex, such as several genes involved in inflammation, have also been associated with alopecia areata.

Some of the genetic variations associated with alopecia areata have been identified in people with other autoimmune disorders, which suggests that this group of diseases may share some genetic risk factors. People with alopecia areata have an increased risk of developing other autoimmune disorders, including vitiligo, systemic lupus erythematosus, atopic dermatitis, allergic asthma, and autoimmune thyroid diseases (such as Hashimoto thyroiditis and Graves disease). Similarly, people with those autoimmune disorders have an increased risk of developing alopecia areata.

In many cases, it is unknown what triggers hair loss in people with alopecia areata. It is possible that environmental factors, such as emotional stress, physical injury, or illness, provoke an abnormal immune response in people who are at risk. However, in most affected people, the onset of hair loss has no clear explanation.

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Genes linked with sunburn, skin cancer risk

 

May 8, 2018

Certain genes can determine which people are more at risk of getting sunburn and possibly develop skin cancer as a result..

In a trawl of the genetics of nearly 180,000 people of European ancestry in Britain, Australia, the Netherlands and United States, researchers found 20 sunburn genes.

Eight of the genes had been associated with skin cancer in previous research, according to findings published in the journal Nature Communications.

And in at least one region of the genome, “we have found evidence to suggest that the gene involved in melanoma risk… acts through increasing susceptibility to sunburns,” co-author Mario Falchi of King’s College London told AFP.

Sun exposure is critical for the body’s production of vitamin D, which keeps bones, teeth, and muscles healthy, and which scientists say may help stave off chronic diseases, even cancer.

But too much can be painful in the short-term, and dangerous for your health.

The new study, which claims to be the largest to date into the genetics of sunburn, helps explain why people with the same skin tone can have such different reactions to exposure to sunlight—some burn red while others tan brown.

It may also begin to explain factors in skin cancer risk.
“It is necessary to explore these genes in more detail, to understand the mechanism by which they contribute to propensity to burn,” said Falchi.

In future, the research may help identify people at risk, through genetic testing.

“People tend to ‘forget’ that sunburns are quite dangerous,” said Falchi.

“Given the rise in incidence in skin cancer, we hope that knowing there is a genetic link between sunburn and skin cancer may help in encouraging people to lead a healthy lifestyle.”

More information: Genome-wide association study in 176,678 Europeans reveals genetic loci for tanning response to sun exposure, Nature Communications (2018).
nature.com/articles/doi:10.1038/s41467-018-04086-y
Journal reference: Nature Communications

Genetic Testing for Breast Cancer – Mayo Clinic

It could be your mom, sister, aunt or best friend. One out of 8 women will get breast cancer in her lifetime. A small subset of the women who get diagnosed have inherited an abnormal copy of a gene that runs in families and can greatly increase their risk of certain cancers. One question these women and their families face is, “Should I get tested to find out if I have a genetic risk?” The answer is always a very personal one.

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