A case report on filamin A gene mutation and progressive pulmonary disease in an infant

A lung tissued derived mesenchymal stem cell study

Valeria Calcaterra, Maria Antonietta Avanzini, Melissa Mantelli, Emanuele Agolini, Stefania Croce, Annalisa De Silvestri, Giuseppe Re, Mirella Collura, Alice Maltese, Antonio Novelli, Gloria Pelizzo

Research output: Contribution to journalArticle

Abstract

RATIONALE: Mesenchymal stem cells (MSC) play a crucial role in both the maintenance of pulmonary integrity and the pathogenesis of lung disease. Lung involvement has been reported in patients with the filamin A (FLNA) gene mutation. Considering FLNA's role in the intrinsic mechanical properties of MSC, we characterized MSCs isolated from FLNA-defective lung tissue, in order to define their pathogenetic role in pulmonary damage.

PATIENT CONCERNS: A male infant developed significant lung disease resulting in emphysematous lesions and perivascular and interstitial fibrosis. He also exhibited general muscular hypotonia, bilateral inguinal hernia, and deformities of the lower limbs (pes tortus congenitalis and hip dysplasia). Following lobar resection, chronic respiratory failure occurred.

DIAGNOSIS: Genetic testing was performed during the course of his clinical care and revealed a new pathogenic variant of the FLNA gene c.7391_7403del; (p.Val2464AlafsTer5). Brain magnetic resonance imaging revealed periventricular nodular heterotopia.

INTERVENTIONS AND OUTCOMES: Surgical thoracoscopic lung biopsy was performed in order to obtain additional data on the pathological pulmonary features. A small portion of the pulmonary tissue was used for MSC expansion. Morphology, immunophenotype, differentiation capacity, and proliferative growth were evaluated. Bone marrow-derived mesenchymal stem cells (BM-MSC) were employed as a control. MSCs presented the typical MSC morphology and phenotype while exhibiting higher proliferative capacity (P <.001) and lower migration potential (P=.02) compared to control BM-MSC.

LESSONS: The genetic profile and altered features of the MSCs isolated from FLNA-related pediatric lung tissue could be directly related to defects in cell migration during embryonic lung development and pulmonary damage described in FLNA-defective patients.

Original languageEnglish
Pages (from-to)e13033
Number of pages6
JournalMedicine
Volume97
Issue number50
DOIs
Publication statusPublished - Dec 2018

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Filamins
Mesenchymal Stromal Cells
Lung Diseases
Lung
Mutation
Genes
Periventricular Nodular Heterotopia
Bone Marrow
Hip Dislocation
Muscle Hypotonia
Inguinal Hernia
Genetic Testing
Respiratory Insufficiency
Embryonic Development
Cell Movement
Lower Extremity
Fibrosis
Maintenance

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A case report on filamin A gene mutation and progressive pulmonary disease in an infant : A lung tissued derived mesenchymal stem cell study. / Calcaterra, Valeria; Avanzini, Maria Antonietta; Mantelli, Melissa; Agolini, Emanuele; Croce, Stefania; De Silvestri, Annalisa; Re, Giuseppe; Collura, Mirella; Maltese, Alice; Novelli, Antonio; Pelizzo, Gloria.

In: Medicine, Vol. 97, No. 50, 12.2018, p. e13033.

Research output: Contribution to journalArticle

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AU - Agolini, Emanuele

AU - Croce, Stefania

AU - De Silvestri, Annalisa

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AU - Novelli, Antonio

AU - Pelizzo, Gloria

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SN - 0025-7974

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