Unlocking the Mystery of Hereditary Gelsolin Amyloidosis: A Korean Family's Genetic Journey
"Whole-exome sequencing (WES) reveals a rare p.D214Y mutation in the GSN gene, marking the first reported case of HGA in a Korean family and offering new hope for diagnosis and treatment."
Hereditary gelsolin amyloidosis (HGA), also known as familial amyloidosis of the Finnish type (FAF), is a rare, autosomal dominant amyloidosis. This means it's passed down through families and only one copy of the mutated gene is needed to cause the condition. HGA is characterized by a trio of distinctive symptoms: corneal lattice dystrophy (an eye disorder), peripheral neuropathy (nerve damage affecting the limbs), and cutis laxa (loose, sagging skin).
While HGA has been identified in various ethnic groups worldwide, including Finnish, Japanese, and Danish families, it had never been reported in Korean patients until now. The typical onset of HGA occurs in the third or fourth decade of life, initially presenting with corneal lattice dystrophy. Over time, individuals develop cutis laxa and slowly progressive neuropathy, leading to a range of debilitating symptoms.
This article delves into the groundbreaking case of a Korean family diagnosed with HGA through advanced whole-exome sequencing (WES). We'll explore how the identification of a specific genetic mutation, p.D214Y in the gelsolin (GSN) gene, not only provided a definitive diagnosis for this family but also highlights the increasing role of WES in diagnosing rare and complex neuropathies.
The Diagnostic Puzzle: Unraveling the Symptoms
The index patient, a 58-year-old Korean male, presented with a constellation of concerning symptoms, including involuntary facial twitching, progressive bilateral facial weakness, and tongue atrophy. These symptoms had been gradually worsening over four years, since the age of 54. Compounding the diagnostic challenge, his mother, maternal uncle, two sisters, and son exhibited similar symptoms, pointing towards a possible hereditary condition.
- Nerve conduction study (NCS): Revealed reduced compound muscle action potential (CMAP) amplitudes and conduction velocity in the left facial nerve.
- Electromyography (EMG): Showed reduced recruitment of motor unit action potential in specific muscles.
- Autonomic function tests (AFTs): Indicated sympathetic skin response abnormalities.
The Power of WES: A New Era for Diagnosing Rare Diseases
This case marks the first reported instance of HGA in a Korean family and highlights the crucial role of WES in diagnosing rare and often misdiagnosed conditions. While traditional diagnostic approaches rely on recognizing specific clinical features, the phenotypic manifestations of HGA can vary, making diagnosis challenging.
WES offers a powerful alternative, allowing clinicians to identify the underlying genetic cause, even in the absence of classic symptoms. In this case, WES not only confirmed the diagnosis of HGA but also facilitated genetic counseling for the family, enabling them to understand the inheritance pattern and assess the risk for future generations.
The successful diagnosis of HGA in this Korean family underscores the transformative potential of genomic medicine. As WES becomes more accessible and affordable, it is poised to play an increasingly important role in diagnosing and managing a wide range of rare and complex genetic disorders, offering hope for improved outcomes and personalized treatment strategies.