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The FLNC mutation that we identified is distinct in terms of the associated phenotype, muscle morphology, and underlying molecular mechanism, thus extending the currently recognized clinical and genetic spectrum of filaminopathies. We conclude that filamin C is a dosage-sensitive gene and that FLNC haploinsufficiency can cause a specific type of myopathy in humans.

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Aims: In the current study we aimed to explore the prevalence of gastrointestinal (GI) manifestations in hereditary transthyretin amyloid (hATTR) amyloidosis associated with Glu89Gln mutation. Methods: We recruited 78 patients with hATTR amyloidosis associated with Glu89Gln mutation. The diagnosis of hATTR was defined by a documented transthyretin mutation through DNA analysis. Symptoms were recorded as present or absent at the time of enrollment into the study. The gastrointestinal (GI) symptoms checklist included the following items: early satiety, nausea, vomiting, constipation, alternating diarrhea/ constipation, diarrhea, fecal incontinence and unintentional weight loss. Results: Forty-two patients (53.8%) reported at least one GI symptom or sign. Diarrhea was the most frequently reported (30.8%), followed by unintentional weight loss (28.2%) and nausea (21.8%). Fecal incontinence (3.8%) was the least common one. No significant gender related difference in overall GI symptom prevalence was found (females 52.16%, males 55%, p = 0.834). Type of disease onset was not related to GI prevalence (earlyonset 50%, late-onset 55.6%, p=0.650). After dividing the patients into groups with a disease duration of <5 years, 5–10 years and >10 years, respectively, the prevalence of GI symptoms was found to be significantly higher in later stages (26.3% vs. 55.0% vs. 78.9%, p = 0.005; OR 2.450, 95% CI 1.084-5.538). Gastrointestinal manifestations had no impact on survival (p=0.193). Conclusions: Gastrointestinal manifestations are very common in hATTR patients with Glu89Gln mutation and increase with disease duration. They are not associated with gender and onset of the disease and have no impact on patient survival. These results highlight the importance of a thorough evaluation of the GI function in patients with ATTR amyloidosis and should stimulate further studies on the phenotypic differences related to genotype and geographic origin.