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Two hitherto unknown mutations in the CLN5 gene were originally reported CLN5 disease, a form of late childhood Batten disease, in a new study.

The study also represents the second publication to describe CLN5 disease in people in Pakistan, hinting at a more global distribution of the disease than previously thought.

The results, “New disease-causing CLN5 variants identified in Pakistani patients with neuronal ceroid lipofuscinosis, ”Were published in the Journal of Neurological Sciences.

Late infantile Batten disease refers to Batten disease in which symptoms start in childhood, usually between 2 and 8 years of age. CLN5 disease is a form of late childhood Batten disease caused by mutations in the gene. CLN5.

Disease was originally identified in populations of northern Europe in the late 1990s. Since then, research has shown that this disease is also present elsewhere in the world.

The new study describes two Pakistani families affected by CLN5 disease. In both families, the parents were inbred (biologically related to each other).

In one family, the two oldest were affected: a 10-year-old girl and a 7-year-old boy. Both children experienced a similar progression of symptoms, including memory loss, difficulty moving, vision loss, and speech disturbances, which started appearing at age 6-7 and progressed. with time.

Genetic testing in this family revealed that the affected children had a mutation in CLN5 that had not been previously reported. This mutation was called c.477T> C or p.Cys159Arg, referring to the change in DNA and protein, respectively.

The children were homozygous for this mutation – that is, the mutation was present in both of their copies of the CLN5 gene (one copy of each biological parent). Their unaffected siblings and parents were determined to be heterozygous; they had a mutated copy of CLN5, and a wild type copy.

The disease is inherited in an autosomal recessive fashion, which means that a person will only develop the disease if they have two mutant versions of CLN5. People who have only one copy are said “”carriers. “This means that they themselves are not affected, but are at risk of passing the mutated gene to their biological children, who could develop the disease if they also inherit a second mutant gene from the other parent. organic.

In the second family, a 10-year-old boy started having seizures when he was 6 years old. Over time, the seizures worsened and the boy also suffered memory loss, visual impairment and reduced motor skills.

Genetic testing revealed the boy was homozygous for a previously unreported mutation called c.925_926del or p.Leu309AlafsTer4. Her parents were both heterozygous carriers.

Computer modeling of these two newly described mutations suggested that both mutations significantly impaired the function of the protein encoded by CLN5. This is consistent with these mutations causing CLN5 disease.

“In the two Pakistani families, we identified two new homozygous variants of CLN5,” the study authors wrote, noting that “our subjects are also the second cases of CLN5 in the Pakistani population”, following a previous report published in 2009.

This suggests that CLN5 disease may be more prevalent around the world than previously thought.

“To date, most cases of CLN5 disease have been described in Finnish and [northern] European countries as well as Italy and China, ”the authors wrote. “Our results indicate that pathogenic CLN5 variants are also present in the South Asian region of Punjab, leading to a more global distribution of CLN5 disease.”