Description

Copyright infringement not intended

Picture Courtesy: Timesnow

Context:

In a study published in the New England Journal of Medicine, researchers described the first successful in-utero treatment for spinal muscular atrophy (SMA), a fatal genetic disorder.

About Spinal Muscular Atrophy (SMA)

SMA is a genetic neurodegenerative disorder caused by mutations in the SMN1 gene, leading to a deficiency of the survival motor neuron (SMN) protein.

SMN protein is essential for motor neurons in the spinal cord, which control muscle movement. Without it, muscles waste away, causing progressive weakness. The most severe form, SMA type 1, results in death by age 2–3 if untreated.

Prevalence: Affects 1 in 10,000 births.

Mechanism: Mutations in SMN1 disrupt motor neuron function, leading to muscle atrophy.

How Was SMA Treated in the Womb?

Patient Background

The parents, both carriers of SMA genetic variants, had previously lost a child to SMA type 1. Genetic testing via amniocentesis confirmed their second fetus had no SMN1 gene copies, indicating a high risk of SMA type 1.

Treatment Protocol

Scientists used risdiplam (brand name: Evrysdi), an oral drug that boosts SMN protein production by activating the SMN2 gene. Normally administered after birth, risdiplam was given prenatally for the first time:

The mother took risdiplam daily from 32 weeks of pregnancy for six weeks.
The baby began treatment at 1 week old and will likely continue lifelong.

Outcome

After 30 months, the child shows no signs of SMA, with normal muscle development and higher SMN protein levels than typical SMA patients.
Early intervention likely preserved motor neuron function, preventing irreversible damage.

Must Read Articles:

Mutations in Cabbage

JN.1 with L455S "FLip" mutation

Source:

INDIAN EXPRESS

PRACTICE QUESTION

Q.Consider the following statements in the context of the consequences of genetic mutations:

Most spontaneous mutations in somatic cells lead to heritable changes in the organism's offspring.
Mutations in regulatory regions of genes can alter the level and timing of gene expression without changing the protein sequence.
Beneficial mutations are extremely rare and play a negligible role in the long-term evolutionary adaptation of species.
The severity of a genetic disease caused by a mutation is solely determined by the type of mutation and not by the specific gene or protein affected.

How many of the above statements are correct?

A) Only one

B) Only two

C) Only three

D) All four

Answer: A

Explanation:

Statement 1 is incorrect. Somatic mutations occur in non-reproductive cells. These mutations are confined to the individual in which they occur and are not passed onto offspring (i.e., they are not heritable). Only mutations in germline cells (sperm and egg cells or their precursors) are heritable.

Statement 2 is correct. Regulatory regions control when, where, and how much a gene is expressed. Mutations in these regions (promoters, enhancers, silencers, etc.) can drastically alter gene expression levels (upregulation or downregulation) or change the timing of expression. This can have significant phenotypic consequences even if the protein-coding sequence itself remains unchanged.

Statement 3 is incorrect. While beneficial mutations are less frequent than neutral or harmful mutations, they are crucial for evolution. Beneficial mutations provide a selective advantage in a given environment. Over long periods, these mutations are favored by natural selection, leading to adaptation and the evolution of species. They are not negligible; they are the driving force of adaptive evolution.

Statement 4 is incorrect. The severity of a genetic disease is not solely determined by the type of mutation. While mutation type (frameshift, nonsense, etc.) is important, the specific gene and protein affected are equally, if not more, critical. A missense mutation in a critical enzyme's active site might be more severe than a frameshift mutation in a non-essential gene. The functional importance of the gene, the protein's role, and the location of the mutation within the protein all contribute to disease severity.