At present, it is unknown how different mutations of TBC1D24 cause non-syndromic deafness (DFNB86, OMIM 614617), epilepsy (OMIM 605021), epilepsy with deafness, or DOORS syndrome (OMIM 220500) that is characterized by deafness, onychodystrophy (alteration of toenail or fingernail morphology), osteodystrophy (defective development of bone), mental retardation, and seizures.
Bi-allelic TBC1D24 pathogenic variants are known to cause nonsyndromic deafness, epileptic disorders, or DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, seizures).
More information is needed to understand the cellular roles of TBC1D24 and identify the genes responsible for DOORS phenotypes in individuals who do not have a mutation in TBC1D24.
More information is needed to understand the cellular roles of TBC1D24 and identify the genes responsible for DOORS phenotypes in individuals who do not have a mutation in TBC1D24.
More information is needed to understand the cellular roles of TBC1D24 and identify the genes responsible for DOORS phenotypes in individuals who do not have a mutation in TBC1D24.
More information is needed to understand the cellular roles of TBC1D24 and identify the genes responsible for DOORS phenotypes in individuals who do not have a mutation in TBC1D24.
More recently, TBC1D24 mutations have been shown to cause a variable range of disorders, including epilepsy of various seizure types and severity, non-syndromic deafness, and DOORS syndrome.
Mutations in TBC1D24 have been linked to a variety of epileptic syndromes and recently to syndromic hearing impairment DOORS syndrome and nonsyndromic hearing impairment DFNB86.
Mutations in TBC1D24 are described in patients with a spectrum of neurological diseases, including mild and severe epilepsies and complex syndromic phenotypes such as Deafness, Onycodystrophy, Osteodystrophy, Mental Retardation and Seizure (DOORS) syndrome.
Mutations in another BAF complex gene (SMARCA2) and (TBC1D24) were found to cause clinically similar conditions with ID, Nicolaides-Baraitser syndrome and DOORS syndrome, respectively.
Mutations in the Tre2/Bub2/Cdc16 (TBC)1 domain family member 24 (TBC1D24) gene are associated with a range of inherited neurological disorders, from drug-refractory lethal epileptic encephalopathy and DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, seizures) to non-syndromic hearing loss.
Mutations that disrupt the <i>TBC1D24</i> presynaptic protein have been implicated in various neurological disorders including epilepsy, chronic encephalopathy, DOORS (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures) syndrome, nonsyndromic hearing loss, and myoclonus.
Other variants in TBC1D24 have been associated with a panoply of clinical symptoms including autosomal recessive NSHL, syndromic hearing impairment associated with onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS syndrome), and a wide range of epileptic disorders.
Sanger sequencing was negative for the DOORS syndrome gene TBC1D24 but exome sequencing identified a homozygous deletion in UBE3B (NM_183415:c.3139_3141del, p.1047_1047del) located within the terminal portion of the HECT domain.