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Progeria

Many people dream of growing up, having a career and finding love, spending their life with the person they choose. Some people do not get that. People born with the genetic mutation known as progeria begin aging unusually fast beginning in infancy or childhood.

Progeria, also known as Hutchinson-Guilford Syndrome, is a very uncommon genetic mutation that causes accelerated aging beginning in infancy and resulting in death usually by the age of 13. This mutation does not have familial ties, as it is a completely random protein mutation. It affects about 1 in 4 million newborns worldwide. Image 1. Image of a child affected by Progeria.

Symptoms and Treatment:

The symptoms associated with Progeria are complete hair loss, thinning skin with wrinkles and visible veins, small face proportions for head size, a high-pitched voice, prominent eyes, slow growth including a below-average height and weight, and a narrow face with a beak-like nose and small jaw. Some more serious symptoms include resistance to insulin, skeletal abnormalities and fragile bones, delayed and abnormal tooth formation, hardening and tightening of the skin, lack of muscle mass and fat under the skin, and severe cardiovascular disease.

Symptoms typically begin within 1 year of the affected child's life. These symptoms are a result of an abnormal formation of the lamin A protein, then referred to as Progerin. The first signs noticed are that the child will appear to be much smaller than other children their age. There is currently no treatment available to cure this Progeria, however, there are medications that can slow the progression of the symptoms.

Cause:

Progeria is caused by a mutation in the LMNA gene. Two main products resulting from this gene are called Lamin A and Lamin C. Progeria is caused when a mutation “replaces the nucleotide cytosine with the nucleotide thymine at position 1824 (written as C1824T)” (LMNA gene). This minute change alters the product from Lamin A to Progerin. Progerin is 50 amino acids shorter than Lamin A, making it likely to produce other mutations as well.

The malformed protein is then incorporated into the lamina of the nuclear membrane. This warps its shape, and over time, the buildup of this malformed protein causes damage to the nucleus. The nucleus is where all our genetic information is stored. When it is damaged, the information starts to break down in a way that happens naturally in old age. Progerin is used in the natural aging process later on in life, to break down the information. The symptoms of Progeria are similar to those you see in the elderly because the process is the same. It simply happens too soon and much faster due to the uncontrolled production and buildup of the Progerin.

Image 2. Indicated section where the mutation takes place.

Inheritance and Frequency:

Progeria is an extremely uncommon disorder. It gets diagnosed to 1 in 4 million newborns. There is no relation to family inheritance, as it is a completely random mutation that occurs in the LMNA gene.

Most people with Progeria die within their first 13 years of life, so there has been no way to see if they would pass the mutation, or even be able to reproduce. It is unlikely that a female with Progeria would be able to withstand bringing a child to term, or giving birth. This is because by the time they are able to reproduce they are at the end of their life span and have "aged" so much that they would be too weak.

Progeria is unlikely to be inherited, even if one of your children already have it. The chance of another one of your children with the same partner is only 2-3%.

References:

"About Progeria". NIH National Human Genome Research Institute. December 27, 2013. Sep. 3, 2019

Bocchini, Carol A. (2018) “LAMIN A/C; LMNA” OMIM

"Hutchinson-Gilford progeria syndrome". NIH US National Library of Medicine. Sep. 3, 2019. Sep. 3, 2019

“LMNA gene”. NIH US National Library of Medicine. Sep. 3, 2019. Sep. 3, 2019

"Progeria". Mayo Clinic. Sep. 3, 2019

"Progeria". NIH National Center for Advancing Translational Sciences. Sep. 1, 2019. Sep. 3, 2019

“Progeria | Definition, Types, Symptoms, & Facts|. Google images. https://www.britannica.com/science/progeria

"Progeria 101/FAQ". Progeria Research Foundation). Sep. 3, 2019

"Progerin, damaged telomeres and aging?" ,The Company of Biologists,vol. 123 no. 15, e1502 (2010)

Sinha, Jitendra K.; Ghosh, Shampa; & Raghunath, Manchala (2014). "Progeria: A rare genetic premature ageing disorder . IJMR Indian Journal of Medical research.

The role of genetic mutations in genes LMNA, PPARG, PLIN1, AKT2, CIDEC in Köbberling–Dunnigan Syndrome. Google Images. https://www.heighpubs.org/jgmgt/jgmgt-aid1004.php

“What is Cardiovascular Disease?”. American Heart Association. May 31, 2017. Sep. 3, 2019

“What is a gene mutation and how do mutations occur?” NIH US National Library of Medicine. Sep. 3 2019. Sep. 3, 2019

“What is Insulin”. Hormone Health Network. Nov. 2018. Sep. 3, 2019