FLNA p.V528M substitution is neither associated with bilateral periventricular nodular heterotopia nor with macrothrombocytopenia

• Published in: Journal of human genetics Vol. 55; no. 12; pp. 844 - 846
• Main Authors: Kunishima, Shinji, Ito-Yamamura, Yoshimi, Hayakawa, Akira, Yamamoto, Toshimichi, Saito, Hidehiko
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2010; Nature Publishing Group
• Subjects: 631/208/737; 692/699/1541; 692/699/375; Actin; Adult; Amino Acid Substitution; Autopsy; Bernard-Soulier Syndrome - genetics; Biomedical and Life Sciences; Biomedicine; Cell migration; Child; Child, Preschool; Contractile Proteins - genetics; Cytoplasm; DNA Mutational Analysis; Female; Filaments; Filamins; Gene Expression; Gene Frequency; Gene Function; Gene Therapy; Genetic Diseases, X-Linked - genetics; Human Genetics; Humans; Male; Microfilament Proteins - genetics; Molecular Medicine; Neurodevelopmental disorders; Nodules; Pedigree; Periventricular Nodular Heterotopia - genetics; Platelets; short-communication; Substantia grisea; Thrombocytopenia; Thrombocytopenia - genetics; Ventricle (lateral); macrothrombocytopenia; periventricular heterotopia; p.V528M
• ISSN: 1434-5161; 1435-232X; 1435-232X
• DOI: 10.1038/jhg.2010.114

Filamin A is encoded by the FLNA gene on chromosome Xq28 and functions in cross-linking actin filaments into orthogonal networks in the cortical cytoplasm. FLNA p.V528M was initially detected in a female autopsy case of X-linked bilateral periventricular nodular heterotopia (BPNH), a neuronal migration disorder characterized by subependymal nodules of gray matter. During our mutation analysis of FLNA in a boy with apparent X-linked thrombocytopenia, we detected the p.V528M variant. The patient, mother and sister, who were heterozygous for the substitution, did not have BPNH. We observed an allele frequency of 4.8% in healthy control Japanese, but did not observe the variant in Caucasian subjects. Hemizygous controls had a normal platelet count and size. We suggest that p.V528M is neither associated with BPNH nor with thrombocytopenia and giant platelets, and represents a functional polymorphism.