FAM111B Gene Mutations Not Associated with Scleroderma, Study Finds

José Lopes, PhD avatar

by José Lopes, PhD |

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Mutations in the FAM111B gene are rare in scleroderma patients and not associated with disease development, according to new research.

This finding was reported in the study, “Mutations of FAM111B gene are not associated with Systemic Sclerosis,” published in the journal Scientific Reports.

Although scleroderma has low heritability, family history of the disease is the strongest risk factor for its development, as shown by the 15-fold greater risk in siblings of affected individuals. Identified susceptibility genes for scleroderma belong to one of three categories: immune responses, vasculopathy (any disease affecting blood vessels), and fibrosis, or scarring.

At least six mutations in FAM111B gene have been associated with hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP), a rare disorder particularly affecting skin, muscles, lungs and pancreas, and sharing clinical similarities with scleroderma.

Aiming to find out if mutations in FAM111B are also present in scleroderma, a team led by researchers from the University of Cape Town in South Africa performed blood DNA analysis in 131 South African patients — 118 women and 13 men, 73 with diffuse cutaneous and 58 with limited cutaneous scleroderma.

Of these patients, who had a mean age at diagnosis was 47.2 years, 78 (59.5%) were black Africans.

Most patients analyzed had Raynaud’s phenomenon (90.1%) — characterized by numb, prickly and frigid fingers and toes in response to cold temperatures or stress — and were positive for antinuclear factor antibody (ANA; 90.4%), which is a marker for autoimmune diseases.

The modified Rodnan skin score — a measure of skin thickness — was significantly higher in patients with diffuse cutaneous scleroderma. Musculoskeletal manifestations, including tendon friction rubs, joint contractures, muscle weakness, and elevated creatine kinase (an indicator of myopathy and kidney injury), were also more common in patients with the diffuse cutaneous type than in those with limited cutaneous scleroderma.

Genetic analysis showed two FAM111B genetic variants in the group analyzed.

The c.917 A > G variant (rs200497516) was detected in one patient with scleroderma and in one of 243 healthy controls from the general South African population. Bioinformatic tools predicted this variant to be benign, making it unlikely to impact FAM111B structure and/or function.

The other FAM111B variant, c.988 C > T (rs35732637), was found in three scleroderma patients, but also in 42 (17.3%) controls, and is a known polymorphism, or gene variant.

Therefore, the team suggested that in contrast to POIKTMP, genetic variants in FAM111B do not seem to contribute to scleroderma development.

“Our findings of a missense variant and a known polymorphism with no functional or structural impact on FAM111B suggest that, in this cohort, FAM111B gene mutations are not associated with [scleroderma],” the researchers wrote.