A dual phenotype of periventricular nodular heterotopia and frontometaphyseal dysplasia in one patient caused by a single FLNA mutation leading to two functionally different aberrant transcripts.

ABSTRACT: Two disorders, periventricular nodular heterotopia (PVNH) and a group of skeletal dysplasias belonging to the oto-palato-digital (OPD) spectrum, are caused by FLNA mutations. They are considered mutually exclusive because of the different presumed effects of the respective FLNA gene mutations, leading to loss of function (PVNH) and gain of function (OPD), respectively. We describe here the first patient manifesting PVNH in combination with frontometaphyseal dysplasia, a skeletal dysplasia of the OPD-spectrum. A novel de novo mutation, 7315C-->A in exon 45 of the FLNA gene, was identified. It leads to two aberrant transcripts, one full-length transcript with the point mutation causing a substitution of a highly conserved leucine residue (L2439M) and a second shortened transcript lacking 21

SUBMITTER: Zenker M 

PROVIDER: S-EPMC1181949 | biostudies-literature | 2004 Apr

REPOSITORIES: biostudies-literature