The Gene Behind CLN4: DNAJC5
The DNAJC5 gene, on chromosome 20, makes a protein called cysteine string protein alpha (CSPα). Nerve cells use CSPα to keep the machinery of communication working. It refolds misshapen proteins so they can be reused.
In CLN4, a change in DNAJC5 produces an altered CSPα that can’t do its job. Communication between nerve cells breaks down, waste material builds up inside cells, and nerve cells gradually die. Most known disease-causing changes fall in one region of the gene, called the cysteine-string domain.
How CLN4 Is Inherited
CLN4 is the only form of Batten disease inherited in an autosomal dominant pattern. Every other form is recessive, meaning a child must inherit an altered gene from both parents.
“Autosomal dominant” means one altered copy of DNAJC5 is enough to cause CLN4. Because the gene is not on a sex chromosome, men and women are affected equally.
| Family member | Chance of inheriting the DNAJC5 variant |
|---|---|
| Child of a person with CLN4 | 50 percent, for each child |
| Brother or sister of a person with CLN4, when a parent has the variant | 50 percent |
| Person with no family history | Possible but rare, through a new (de novo) variant |
About CLN4 Batten Disease
How CLN4 Progressees
Most people diagnosed with CLN4 have an affected parent. CLN4 can appear to skip a generation when a parent died before symptoms began, or when a parent’s symptoms were never recognized as CLN4.
How CLN4 Is Diagnosed
- Medical and family history. A neurologist reviews symptoms and takes a family history covering at least three generations, looking for early dementia, epilepsy, or early death.
- Neurological tests. Brain MRI and EEG help assess changes in the brain and seizure activity.
- Genetic testing. A multigene panel, exome sequencing, or genome sequencing looks for a disease-causing change in DNAJC5.
- Genetic counseling. A genetics professional explains the result and what it means for relatives.
Before genetic testing was available, adult Batten disease was usually diagnosed from tissue samples examined under a microscope. That is how Dennis LaBarge was diagnosed, about four years after his first seizures.
Some DNAJC5 changes are hard to detect. In one documented family, a duplication in the gene was missed by both standard sequencing and exome sequencing. If CLN4 is strongly suspected and testing is negative, ask whether more specialized testing is needed.
Genetic Counseling for Families
A CLN4 diagnosis affects the whole family. A genetic counselor can help relatives:
- Understand their own risk and decide whether, and when, to have genetic testing
- Think through what a positive or negative result would mean before testing
- Explore family planning options, including prenatal and preimplantation genetic testing, once the family’s variant is known
The Genetic Information Nondiscrimination Act (GINA) protects Americans from genetic discrimination in health insurance and most employment. It does not cover life, disability, or long-term care insurance, and it does not apply to employers with fewer than 15 employees. Some states offer more protection. Learn about GINA from the National Human Genome Research Institute.
Frequently Asked Questions
Can CLN4 skip a generation?
It can appear to, when a parent died young or their symptoms were not recognized. A true skip would require reduced penetrance, which has not been widely reported in CLN4.
If I inherit the DNAJC5 variant, will I develop CLN4?
CLN4 has high penetrance, which means most people who inherit a disease-causing variant are expected to develop symptoms. The age when symptoms begin varies.
Where can I find a genetic counselor?
Ask your neurologist for a referral, or search the National Society of Genetic Counselors’ directory at findageneticcounselor.nsgc.org.
Learn More
Read about CLN4 symptoms and progression, or see how research is targeting the DNAJC5 gene.
This page is general information, not medical or genetic advice. Talk with a genetic counselor about your family’s situation.
Frequently Asked Questions
Does CLN4 cause blindness?
Usually not. Unlike childhood forms of Batten disease, CLN4 does not typically affect the retina.
Can CLN4 progression be slowed?
Not with any approved treatment yet. Researchers are developing individualized therapies that target the gene behind CLN4. See the research we fund.
Help Change the Course of CLN4
Every symptom on this page is a reason we fund research. Support CLN4 research.
This page is general information, not medical advice. Talk with a neurologist or genetic counselor about your situation.
