Sofia had been a shadow of herself since she got married. Getting married had always been something she had looked forward to; even since her early days as a child. It had been 8 years since she got married to Emeka. The wedding bells still rang in her ears. Emeka looked so handsome on that day, all suited up with his hair well trimmed. His smile was amazing. She had always wished for that day. It was blissful; a day she would wish to always relive. It was shocking how quickly things had changed. Now, she had not any reason to smile. Her one true wish had not come to pass. Years had gone by and she had heard the cries of babies everywhere except in her house. She had always wished to hear the cries of a baby in her house. She paid her priest regular visits to ask why this was happening to her. Her priest had always told her to be patient and wait on “god”. “God’s time is the best” – he had always reiterated. Well, with time, she finally got pregnant-again but she even got more scared, more so, due to the fact that she had always experienced miscarriages. This time it was different. There was no miscarriage or at least she thought so. It was safe to assume so since she was already in the third trimester of her pregnancy. The previous ones never made it beyond a month. Her delivery was the biggest talk in town. After eight years, it had to be. The baby was amazing to look at. She had not seen anything more adorable in her life. It was named Magdalene. Everything was finally perfect or so she thought.

A year went by and Magdalene was getting less cute. Sofia did not really pay much of an attention to that as Magdalene was still the best thing to have ever happened to her. She was however worried when people complained that Magdalene’s head was uncharacteristically big for a one-year-old. To her, it was common among children. She, however, got a little worried when she started noticing her daughter’s oddly ageing skin but to her, it was just one of those things. Magdalene was particularly scolded in school even as a four-year-old because she looked weird. She could not grow hair; not even in any part of her body. I mean she had no eyebrows and no eyelashes either. The green veins on her forehead were particularly irritating to a lot of people. People resorted to calling her “The bush baby” as they had never seen a child as weird as her. She was even uglier when she smiled because her teeth were decayed and her ageing skin was a cause for concern. Her fifth birthday had such a low turnout. Sofia was very worried at this point. She resorted to seeing her priest on the issue. The priest suggested an exorcism. He said there was a very high chance “an external being” was living in her and he could most likely cast it out. He assured her this would turn her into a normal child who would not have to go through all that she was going true.

An exorcism was carried out and well, things still remained the same. The priest advised her to wait on “god” again like she did last time. She listened. She got a reality check when Magdalene turned 13. She had a heart attack and this time, she was taken to the hospital. Sofia was so scared at this point. She could not bear losing her only child especially after eight years of not having one. She did not understand why this was happening to her in the first place. The doctor said she had an extremely rare condition. She had never heard that before. Wtf was Progeria. She was lost when he uttered something that sounded like Hutchinson-Gilford Progeria Syndrome. The doctor told her the symptoms her daughter was experiencing were notably seen in patients with Progeria and her condition had no cure. Magdalene would later die from that heart attack.

So What The Hell is Progeria ?

Progeria simply indicates premature ageing. It is a condition where children age in an uncharacteristic fashion. I mean this is a condition where you have children looking like old people but behaving as children. A mutation that occurs at the embryonic stage of development presents as accelerated ageing later in life. Hutchinson first mentioned this disease in 1886 but Gilford gave a much more detailed explanation of this disease.

This condition is an autosomal dominant disorder with an incidence of 1 in 4 million people so it is quite rare. Up until now, only 100 people have been diagnosed with this condition in history so it really is rare. Its symptoms are quite so noticeable. Other than the fact that patients appear to be old, there is a noticeable loss of hair, hair colour, facial cyanosis, failure to thrive and a sharp nose due to the sculptured nasal tip. The worrying part about this condition is the average lifespan is reduced to 13 years. Patients barely make it past their early twenties and considering most of them do not reproduce, it is rarely inheritable.

Progeria just goes on to buttress how bad mutation can be. It is a consequence of mutation – A point mutation to be specific. The LMNA gene codes for lamin A protein which is an integral component of the nuclear lamina. The nuclear lamina protects the contents of the nucleus ensuring chromosomes are protected. In progeria, there is a substitution of cytosine with thymine at codon 608 resulting in the production of an abnormal lamin A protein otherwise known as Progerin. Accumulation of progerin makes the cell much more prone to DNA damage, which probably results in ageing. The proposed underlying mechanism suggests that the farnesyl group attached during the post-translational modification of the lamin A protein is not detached due to the already described point mutation so the resulting protein is abnormal and only destabilizes the nuclear lamina.

This had led to the suggestion and even pre-clinical trials of farnesyltransferase inhibitors. Farnesyltransferase is the enzyme that orchestrates the attachment of a farnesyl group to pre-lamin A during post-translational modification of this protein. It only makes sense to inhibit this enzyme as this will ensure progerin is no longer farnesylated. It has proven quite useful in managing progeria. It has not reduced the cardiovascular risks that accompany progeria so a drug that does this will only need to be introduced. That was done anyway. So far a drug called Lonafarnib has been quite useful in managing progeria. Drugs now are only designed to target the symptoms of progeria and not the disease itself as its underlying mechanisms have not been fully understood.

References

^{(1) https://www.webmd.com/children/progeria#1 (2)https://www.medicinenet.com/progeria_syndrome/article.htm#hutchinson_gilford_progeria_syndrome_facts (3) https://en.wikipedia.org/wiki/Progeria (4) https://onlinelibrary.wiley.com/doi/abs/10.1111/jdv.14827 (5) https://www.fasebj.org/doi/abs/10.1096/fasebj.31.1_supplement.1058.3 (6)http://wprim.whocc.org.cn/admin/article/articleDetail?WPRIMID=664965&articleId=664965 (7) http://www.jocpd.org/doi/abs/10.17796/jcpd.39.2.rn7147700425t647?code=clpd-site (8) https://pdfs.semanticscholar.org/b822/ba6b2de90a945bee4c0c2d5e0bdcab7e7048.pdf}