The FLNA gene is a member of the Filamin (FLN) family, which includes three members: filamin A, filamin B and filamin C. The encoded filamin proteins show 60–80% homology over their entire sequence, except for the two hinge regions. These three proteins are widely expressed during development. The FLNA gene encodes an actin-binding protein called filamin A, which links actin filaments to membrane glycoproteins and crosslinks actin filaments. It plays a role in modeling the cytoskeleton allowing cell shape changes and migration. Filamin A also interacts with transmembrane receptor complexes, integrins, and second messengers. Defects in this protein have been associated with genetic diseases including FG syndrome, frontometaphyseal dysplasia, intestinal pseudo-obstruction, Melnick-Needles syndrome, otopalatodigital syndrome type 1 and 2, periventricular heterotopia, and X-linked cardiac valvular dysplasia.
The FLNA gene has 46 coding exons spanning approximately 26 kb on the X chromosome. This gene has two transcript variants encoding different isoforms. The encoded protein comprises 2647 amino acids with a molecular mass of about 280 kDa. Mutations in this gene have been identified in patients with several syndromes including FG syndrome, frontometaphyseal dysplasia, intestinal pseudo-obstruction, Melnick-Needles syndrome, otopalatodigital syndrome type 1, otopalatodigital syndrome type 2, periventricular heterotopia, and X-linked cardiac valvular dysplasia. Each of these mutations causes specific defects in the filamin A protein resulting inFLNA-related disorders. Frontometaphyseal dysplasia and Melnick-Needles syndrome are caused by "gain-of-function" mutations, which cause an increase in the activity of the filamin A protein or alter its function. a new function. Mutations in exons 3, 4, and 5 have been found in patients with otopalatodigital syndrome type 2, and mutations in exons 11 and 29 have been identified in patients with similar but more severe symptoms.
Eltahir et al., (2016) reported a one-year-old Saudi girl who presented with respiratory distress at birth. At the age of two months she had recurrent cyanotic events, frequent choking while feeding, and significant vomiting. Then she developed recurrent lower respiratory tract infections, bronchospasm, bilateral lung emphysema with basal atelectasis oxygen and mechanical ventilation dependency, and pulmonary artery hypertension. A lung biopsy revealed alveolated lung parenchyma with alveolar simplification. Performing molecular analysis, a heterozygous c.3153dupC variant in exon 21 of the FLNA gene was identified in the affected patient. This pathogenic variant was assumed to be the cause of the disease.
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