Clinical Report: Identification of a homozygous missense mutation in PRPF40B

Overview

This study identifies a homozygous missense mutation, p.Ser166Leu, in the PRPF40B gene associated with essential tremor (ET) in a consanguineous Turkish family. The mutation was found to segregate with ET and is predicted to alter PRPF40B function, which has implications for understanding the genetic basis of ET.

Background

Essential tremor (ET) is a prevalent neurological disorder characterized by kinetic tremors, affecting approximately 1.33% of the global population. The high rate of consanguineous marriages in Turkey has facilitated the discovery of genetic variants associated with neurological disorders, including ET. Understanding the genetic underpinnings of ET can lead to better diagnostic and therapeutic strategies.

Data Highlights

Key Findings

• A homozygous missense variant p.Ser166Leu in PRPF40B was identified in a Turkish family with ET.
• The variant is located within a 7.7 Mb region of homozygosity.
• Four family members were diagnosed with ET, with two also having Parkinson’s Disease.
• Mutant PRPF40B showed altered localization to the nuclear membrane compared to wildtype.
• In silico studies suggest the variant may impact PRPF40B function.

Clinical Implications

The identification of the PRPF40B mutation provides insight into the genetic factors contributing to essential tremor, which may aid in the development of targeted therapies. Clinicians should consider genetic counseling and testing in families with a history of ET, especially in consanguineous populations.

Conclusion

The discovery of the p.Ser166Leu mutation in PRPF40B enhances the understanding of the genetic basis of essential tremor and underscores the importance of genetic studies in familial cases of neurological disorders.

Related Resources & Content

1. Acta Neuropathologica, 2023 -- A familial missense mutation in the SORL1 gene linked to Alzheimer’s disease disrupts its maturation and endosomal trafficking
2. Brain, 2025 -- A recurrent missense mutation in ITPR3 is linked to variable severity in demyelinating Charcot-Marie-Tooth disease
3. Hernia, 2016 -- Identification of a Possible TTN Mutation Through Whole-Exome Sequencing in a Family with Multiple Cases of Inguinal Hernia
4. Consensus Statement on the Classification of Tremors, PMC -- From the Task Force on Tremor of the International Parkinson and Movement Disorder Society
5. Update on Medical Treatments for Essential Tremor, PMC -- An International Parkinson and Movement Disorder Society Evidence‐Based Medicine Review
6. Acta Neuropathologica — Uncommon SQSTM1 Variants Influence Risk for Frontotemporal Lobar Degeneration
7. PRPF40B pre-mRNA processing factor 40B [Homo sapiens (human)] - Gene - NCBI
8. Consensus Statement on the Classification of Tremors. From the Task Force on Tremor of the International Parkinson and Movement Disorder Society - PMC
9. Update on Medical Treatments for Essential Tremor: An International Parkinson and Movement Disorder Society Evidence‐Based Medicine Review - PMC
10. A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor | New England Journal of Medicine
11. Loss-of-function variations in solute carrier family 38 member 6 are associated with essential tremor | Signal Transduction and Targeted Therapy