A novel filamin A D203Y mutation in a female patient with otopalatodigital type 1 syndrome and extremely skewed X chromosome inactivation

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Abstract
Otopalatodigital syndrome type 1 (OPD1) [OMIM 311300] is an X‐linked dominant multiple congenital anomalies disease mainly characterized by a generalized skeletal dysplasia, mild mental retardation, hearing loss, cleft palate, and typical facial anomalies. OPD1 belongs to a group of X‐linked skeletal dysplasias known as oto‐palato‐digital syndrome spectrum disorders that also include OPD2, Melnick–Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). Recently, it has been demonstrated that mutations in the gene encoding the cytoskeletal protein Filamin A (FLNA) are responsible for this group of clinically overlapping human syndromes. We present the phenotypic and molecular data of a sporadic female patient clinically diagnosed with an OPD1 syndrome who carried a novel FLNA point mutation resulting in an Asp203Tyr substitution in the actin‐binding domain of the protein. X‐inactivation analyses demonstrated an extremely skewed pattern towards her maternal chromosome. Our results add to the molecular spectrum of the oto‐palato‐digital related syndromes and contribute to the delineation of phenotype‐genotype correlation in this group of X‐linked skeletal disorders.