Mark ở vũ trụ khác · Another Universe Genes and Rare Diseases #7 · Progeria · The LMNA gene

Progeria: the child who ages fast

Eriksson et al. · Nature · 2003 · and the FDA decision of 20 November 2020

The storytwo doctors start a research foundation for their son's disease
GeneLMNA, which makes lamin A, the mesh that holds the cell nucleus in shape
Todayone drug extends life but does not cure; gene editing tried in mice so far
LabelSolid, with three points that need caution

Source: Eriksson et al. (2003), Nature 423: 293–298; FDA press release, 20/11/2020; Progeria Research Foundation (PRF), "Our story".

For reading and understanding, not a substitute for medical advice.

Re-read in 1 minute

Essence

A very rare diseaseBabies look healthy at birth, then grow slowly, lose hair, and their blood vessels stiffen. Intelligence is not affected.
A family that did not waitIn 1999, two doctors whose son had the disease set up a research foundation, when almost no one studied it.
18 of 20 casesIn 2003 the gene was found: the same single letter changed in LMNA, newly arisen, not passed down by parents.
First drug, 2020The FDA approved lonafarnib. It lowers mortality and extends life, but does not fix the gene.
No cure yetGene editing helped mice live more than twice as long. Not yet in people.

Source: Mayo Clinic (signs, secondary source); PRF "Our story" (1999); Eriksson et al. (2003) (18/20 cases); FDA 20/11/2020; Koblan et al. (2021), Nature 589: 608–614 (mice).

Part 1

The question

Why would a baby age many times faster than other children? And when almost nobody is studying your child's disease, what can a family do?

The question is Mark's, based on the story as told by PRF.

1998–1999A diagnosisNo research, no test. The family starts a foundation.
→
2003The gene is foundOne changed letter in LMNA warps the cell nucleus.
→
2020 to nowFirst drugLonger life, no cure. Gene editing tested in mice.
Part 2

The story

Who, where, when, and why one family had to go looking for answers themselves.

1886 and 1897 · The disease gets a nameTwo English doctors, Jonathan Hutchinson and then Hastings Gilford, described children who aged early. "Progeria" comes from Greek: "pro", before, and "gēras", old age. Today's full name: Hutchinson-Gilford progeria syndrome.
Summer 1998 · A diagnosis in the USSam, son of two doctors, Leslie Gordon and Scott Berns, was diagnosed with progeria at about 22 months old. His parents searched the literature and found almost no research, no diagnostic test and no funding.
Early 1999 · A foundation of their ownThe family gathered relatives, friends and colleagues and founded the Progeria Research Foundation (PRF). The goal: find the cause, then a treatment.
16/4/2003 · The gene is foundA team at the US National Human Genome Research Institute (NHGRI) led by Francis Collins, together with PRF, announced that progeria is caused by mutations in the LMNA gene. Leslie Gordon was a co-author. The paper appeared in Nature in May 2003.
2013 · Sam talks about a happy lifeAt 16, Sam spoke at TEDxMidAtlantic about how he lived: be OK with what you can't do, because there is so much you can do. A documentary about him aired on HBO in October 2013.
10/1/2014 · Sam dies at 17The foundation carried on. By 30 June 2026, PRF had identified 223 children and young adults with progeria or related conditions in 55 countries.

Source: PRF "Our story" (1998, 22 months, 1999, date of death); NHGRI press release 16/4/2003; Eriksson et al. (2003); PRF Quick Facts 30/6/2026 (223 people, 55 countries); Radiopaedia and PRF (1886, 1897, origin of the name, secondary source); TEDxMidAtlantic 2013 talk and the film "Life According to Sam" (secondary sources).

Why is a rare disease hard to study?

The rarer the disease, the fewer patients to study, the fewer cell samples, the less money. Progeria is estimated to affect about 1 in 4 to 8 million births (estimate, secondary source). In 2008, a study that examined 15 children in depth covered nearly half of all known cases at the time.

A family-run foundation can do what a single lab struggles to: find patients worldwide, collect samples, connect researchers.

Source: The Scientist and an ISPOR 2010 conference abstract (estimated rate, secondary sources); Merideth et al. (2008), NEJM (15 children, nearly half of known cases then).

Part 3

How the gene works, in 3 sentences

1. The LMNA gene makes lamin A, a mesh lining the inside of the nuclear envelope that keeps the cell nucleus round and sturdy.

2. Newly made lamin A carries a "fatty tail" (a farnesyl group); normally an enzyme acts like scissors and cuts off the end piece that holds this tail.

3. In progeria, one letter C becomes T, so the cell cuts out 50 amino acids, including the spot where the scissors cut; the faulty protein (progerin) keeps its fatty tail, sticks to the nuclear envelope and slowly warps the nucleus.

Two rows. Top, normal: a prelamin A strand with a fatty tail at its end; scissors cut off the end; mature lamin A sits in a round nucleus. Bottom, progeria: the strand is missing 50 amino acids near the end and the cutting site is gone; the scissors cannot cut; progerin keeps its fatty tail and the nucleus is misshapen. normal fatty tail scissors can cut round nucleuslamin A progeria (C becomes T) 50 amino acids lost no place left to cut warped nucleusprogerin sticksto the envelope
A pair of scissors that cannot find where to cut. The mutation does not change the amino acid at that spot (it is still glycine), but it makes the cell splice the gene's copy in the wrong place, deleting 50 amino acids near the end of the protein. Simplified diagram, not to scale.Source: Eriksson et al. (2003), Nature 423: 293–298 (G608G, GGC to GGT, 50 amino acids); MedlinePlus Genetics (role of lamin A); Yang et al. (2005), PNAS (progerin keeps its farnesyl tail, binds the nuclear envelope).
Timeline of signs. At birth: usually looks healthy. First year: slow growth, hair loss, loss of fat under the skin. Later years: stiff joints, stiffening blood vessels, normal intelligence. Without treatment: death at an average age of 14.5, mostly from heart disease or stroke. at birthusually looks healthy first yearslow growth, hair lossloss of fat under skin later yearsstiff joints and vesselsnormal intelligence about age 14.5average age at deathwithout treatment main cause: heart attack or stroke, like cardiovascular disease in older adults range of age at death without treatment: 6 to 20 years
The body ages fast in blood vessels, skin and bone; the brain does not.Source: Mayo Clinic (birth, first year, intelligence; secondary source); Merideth et al. (2008), NEJM (15 children; skin, joints, bone, blood vessels; death from heart attack or stroke); GeneReviews "Hutchinson-Gilford Progeria Syndrome" (14.5 years, range about 6–20).
Part 4

Fact check: what is true and what is rumour

13 things often said about progeria, checked against original sources. Tap a row to see why.

SOLIDProgeria is caused by a point mutation in the LMNA gene

18 of 20 classic cases had the same single-letter change (GGC to GGT); one more case had a different change in the same codon (Eriksson et al. 2003).

SOLIDChildren with progeria have normal intelligence

Motor development and intelligence are not affected (Mayo Clinic, secondary source). That is one reason not to describe them as "old people in children's bodies".

SOLIDThe main cause of death is cardiovascular disease

Heart attack or stroke (Merideth et al. 2008; GeneReviews).

SOLIDLonafarnib is the first FDA-approved drug for progeria

On 20/11/2020, for patients aged 1 and older; the European Union followed in July 2022 (FDA; EMA).

SOLIDA family-founded charity helped find the gene

PRF and NHGRI announced the gene in 2003; Leslie Gordon co-authored the Nature paper (NHGRI 2003; Eriksson 2003).

CAUTION"The drug adds 2.5 years of life"

That is the average at the longest follow-up (up to 11 years). Over the first 3 years the gain was about 3 months. The comparison was with untreated children from another study, not a randomised trial (FDA, via Contemporary Pediatrics and Fierce Pharma, secondary sources).

CAUTION"Progeria is normal ageing on fast-forward"

There are similarities (stiff vessels, hair loss) but not a full match. Right after the 2008 NEJM paper, three gerontologists wrote a letter objecting to equating the two (letter by Ershler, Ferrucci and Longo).

CAUTION"Progerin is the key to everyone's ageing"

Skin cells from people aged 81–96 carry a little progerin and nuclear defects like progeria (Scaffidi and Misteli 2006). But those were cultured cells; it does not show that progerin drives whole-body ageing.

CAUTION"One in 4 million children has it"

That is an estimate from reviews (about 1 in 4 to 8 million births; secondary sources). The counted number is clearer: PRF has identified 163 people with classic progeria (30/6/2026).

FALSE"Lonafarnib cures progeria"

The drug stops the protein from getting its fatty tail and lowers mortality, but does not fix the gene. Average lifespan with the drug is about 18.7 years (GeneReviews).

FALSE"Parents pass progeria to their children"

The mutation usually arises new in the child, and usually no one else in the family is affected (Eriksson 2003; MedlinePlus Genetics). It is no one's fault.

FALSE"There is already a gene-editing cure for people"

Gene editing worked in mice in 2021 (Koblan et al.). No human gene-editing trial for progeria has been published (checked 16/10/2026).

FALSE"Benjamin Button had progeria"

That is fiction by F. Scott Fitzgerald (1922): the character is born old and grows younger. Progeria does not reverse age and no one "grows young".

Source: as given in each row; full list in Part 9.

Part 5

Where things stand today

From understanding the gene to the first drug, then to gene editing in mice.

2005 · Block the fatty tail, the nucleus looks betterIn mouse cells carrying the progeria mutation, a drug that blocks the enzyme adding the fatty (farnesyl) tail moved progerin off the envelope, and the nuclei blebbed less.
2006 · A little progerin in older peopleSkin cells from people aged 81–96 sometimes use the same faulty splice site as progeria. An intriguing hint, so far in cultured cells.
2018 · Evidence of longer life27 children on lonafarnib were compared with 27 similar untreated children: after about 2.2 years, 1 child (3.7%) versus 9 children (33.3%) had died. Observational, not randomised.
20/11/2020 · FDA approves the first drugLonafarnib, based on 62 patients in two single-arm trials. Europe approved it in July 2022.
2021 · Gene editing in miceOne injection of a "base editor" changed the T back to C; median mouse lifespan rose from 215 to 510 days.
2025–2026 · A second drug in testingProgerinin, an oral drug aimed at progerin, has been in a phase 2 trial since January 2025. No published results, not approved (checked 16/10/2026).
Deaths after a median 2.2 years of follow-up: lonafarnib group 1 of 27 children, 3.7 percent; untreated group 9 of 27 children, 33.3 percent. deaths after about 2.2 years (JAMA 2018) on lonafarnib (27 children) 1 child · 3.7% untreated (27 children) 9 children · 33.3% observational comparison with a group from another study, not a randomised trial
A big difference, but a limited design. With a disease this rare, randomly leaving half the children untreated is hard both ethically and in numbers.Source: Gordon et al. (2018), JAMA 319(16): 1687–1695 (1/27 vs 9/27, median 2.2 years).

Source: Yang et al. (2005), PNAS; Scaffidi and Misteli (2006), Science 312: 1059–1063; Gordon et al. (2018), JAMA; FDA 20/11/2020; EMA, Zokinvy EPAR; Koblan et al. (2021), Nature 589: 608–614 (215 and 510 days); ClinicalTrials.gov NCT06775041 (progerinin); Pharmaceutical Technology 3/2026 (secondary source).

Part 6

Rating

Scores are Mark's assessment based on the sources in Part 9, not figures from a study.

Strength of the gene finding
5/5
Understanding of the mechanism
4/5
Treatment available
2/5
Lesson for readers
4/5
Strengths
  • Gene found fast, 4 years after the foundation began
  • Clear mechanism that led straight to a drug
  • A drug approved by two major regulators
Weaknesses
  • The drug extends life, it does not cure
  • Drug evidence not from randomised trials
  • Gene editing only in mice so far

Label: SOLID. One changed letter in the LMNA gene, and a family that turned grief into a field of research.

More: why does Mark give "treatment" only 2/5?

The drug is real progress: for the first time something helps children live longer. But average lifespan on the drug is still under 20 years, and it has side effects such as nausea, diarrhoea and fatigue. A real cure means fixing the gene, and that has only been done in mice.

Source: GeneReviews (about 18.7 years); FDA 20/11/2020 (common side effects, via AJMC, secondary source); Koblan et al. (2021). The comments are Mark's.

Part 7

Takeaway: reading "this drug helps people live longer" correctly

When you read news about a new drug, three questions help you understand the number.

For reading and understanding, not a substitute for medical advice.

Three questions: compared with whom; followed for how long; average or each person. One more: extends life or cures. 1 · compared with whom?where the controls came fromrandomised or matched 2 · for how long?3 months or 2.5 yearsdepends on the time point 3 · average or each person?average ≠ guaranteedpeople differ 4 · extends or cures?read the exact words"lowers deaths" is not "cures" For the same drug, "3 more months" and "2.5 more years" are both true, at two different time points.
Each question is based on something real in the lonafarnib story.Source: FDA 20/11/2020 (3 months over the first 3 years, 2.5 years at the longest follow-up, via news, secondary source); Gordon et al. (2018) (matched controls). The questions are Mark's suggestions.
Ask "compared with whom"A randomised trial is more reliable than a comparison with a group taken from another study.
Ask "after how long"The number changes with follow-up time. News often picks the nicest number.
Remember "average"A group average promises nothing to one person. Ask the doctor about the specific case.
"Newly arisen" is nobody's faultFor a disease caused by a new mutation, ask a genetics doctor about the risk for a future pregnancy rather than guessing.
Self-check: try it on a health story you read this week

1. Find a story saying something like "drug X helps people live longer / cuts Y by Z%".

2. Does it say what group it was compared with? Write it down.

3. Does it say how long people were followed, and how many? Write it down.

4. Does it say "cures", or "lowers", "extends"? Which word fits the number?

5. Missing two or more of these: treat the story as "needs more reading", not ready to share.

The self-check is Mark's suggestion, not a procedure from a study.

Part 8

Read next

Eriksson et al. (2003), NatureThe paper that found the gene. Short; the abstract is readable.
GeneReviews "Hutchinson-Gilford Progeria Syndrome"Up-to-date medical overview of diagnosis, follow-up and treatment (NCBI Bookshelf).
Sam Berns, "My philosophy for a happy life" (TEDxMidAtlantic 2013)A little over ten minutes, told by Sam himself.
Genes and Rare Diseases #8: Feeling no painAnother gene, an opposite story: people who cannot feel pain, and why pain matters. Read
Part 9

Sources

Main sources are the original paper, FDA and EMA decisions, and medical databases. The working environment blocks NCBI, the FDA and PRF's site, so figures were checked against excerpts of those same pages in search results (16/10/2026), without opening full texts. Secondary sources are labelled.

  1. Eriksson M et al. (2003), "Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome", Nature 423: 293–298, doi 10.1038/nature01629. Deep Blue (U. Michigan)
  2. NHGRI (16/4/2003), press release "Gene for premature aging disorder". genome.gov
  3. Gordon LB et al. (2018), "Association of lonafarnib treatment vs no treatment with mortality rate in patients with Hutchinson-Gilford progeria syndrome", JAMA 319(16): 1687–1695, doi 10.1001/jama.2018.3264.
  4. FDA (20/11/2020), "FDA approves first treatment for Hutchinson-Gilford progeria syndrome and some progeroid laminopathies" (read via AJMC, Fierce Pharma, Contemporary Pediatrics).
  5. EMA, Zokinvy EPAR (authorised in the European Union, July 2022). ema.europa.eu
  6. GeneReviews, "Hutchinson-Gilford Progeria Syndrome", NCBI Bookshelf NBK1121 (read via PubMed abstract 20301300). NCBI Bookshelf
  7. Merideth MA et al. (2008), "Phenotype and course of Hutchinson-Gilford progeria syndrome", New England Journal of Medicine 358. PubMed
  8. Yang SH et al. (2005), mouse study of the progeria mutation with a farnesyltransferase inhibitor, PNAS.
  9. Scaffidi P, Misteli T (2006), "Lamin A-dependent nuclear defects in human aging", Science 312: 1059–1063.
  10. Koblan LW et al. (2021), "In vivo base editing rescues Hutchinson-Gilford progeria syndrome in mice", Nature 589: 608–614, doi 10.1038/s41586-020-03086-7.
  11. MedlinePlus Genetics, "Hutchinson-Gilford progeria syndrome". medlineplus.gov
  12. Progeria Research Foundation, "Our story" and Quick Facts 30/6/2026. progeriaresearch.org
  13. ClinicalTrials.gov NCT06775041, progerinin trial in people with HGPS.
  14. Secondary sources: Mayo Clinic "Progeria" (signs, intelligence); Radiopaedia (origin of the name); The Scientist and ISPOR 2010 abstract (estimated rate); AJMC, Fierce Pharma, Contemporary Pediatrics (details of the FDA decision); Pharmaceutical Technology 3/2026 (progerinin); TEDxMidAtlantic 2013 talk and the film "Life According to Sam" (HBO 2013).