Background:A 24-year-old woman was referred to a neurologist by her general practitioner, because of complaints of headaches and photophobia with intermittent nausea and vomiting for several years. Physical, neurological and laboratory investigations were unremarkable.
Purpose Usher syndrome (USH) is the most common syndromic inherited retinal disease, causing retinitis pigmentosa and sensorineural hearing loss. We reported previously that a nonsense mutation in the centrosome-associated protein CEP250 gene (encoding C-Nap1) causes atypical USH in patients of Iranian Jewish origin. To better characterize CEP250 , we aimed to generate and study a knockout (KO) mouse model for Cep250 . Methods Mice heterozygous for a “knockout-first” Cep250 construct were generated and bred with Cre recombinase mice to generate the null allele and produce homozygous Cep250 KO mice. Retinal function was evaluated by full-field electroretinography (ffERG) at variable ages, and retinal structure changes were examined using histological analysis. Hearing thresholds were detected using auditory brainstem response (ABR) at the age of 20 months. Results The Cep250 KO mouse model was generated by activating a construct harboring a deletion of exons 6 and 7. At 6 months, the ffERG was normal, but it decreased gradually with age. For both photopic and scotopic ffERG responses, very low amplitudes were evident at 20 months. Histological analysis confirmed late-onset retinal degeneration. ABR tests illustrated that hearing threshold significantly increased at the age of 20 months. Conclusions Although most USH animal models have normal retinal function and structure, the Cep250 KO mouse model shows both retinal degeneration and hearing loss with a relatively late age of onset. This model may shed more light on CEP250 -associated retinal and hearing deficits and represents an efficient platform for the development of treatment modalities for USH. Translational Relevance Our study demonstrates better understanding of Cep250 -associated retinal and hearing disease in a mouse model and may help in developing more efficient gene therapy modalities.
Crystal deposit disease is a rare disorder with benign dense soft tissue calcium containing accumulations presenting as pseudogout or tumoral calcinosis. It rarely affects the head and neck region and even less to the petrous bone. We describe a case of para-articular tumoral calcinosis involving the external auditory canal wall in close proximity to the temporomandibular joint with extension towards the middle cranial fossa floor in a 73-year-old man presenting with otalgia and progressing mixed hearing loss. Subtotal petrosectomy with obliteration of the middle ear and mastoid was done with complete removal of the lesion. We discuss the course, treatment and final pathology with possible explanations for the pathophysiology in this particular case. Although tumoral calcinosis is uncommon, this entity should be considered in the differential diagnosis when an osteogenic temporal lesion is seen on computed tomography or magnetic resonance imaging. The treatment for this benign tumor includes complete excision of the lesion in symptomatic cases. Proper evaluation including anamnesis of the family history and previous trauma as well as serology should be done. The exact etiology and classification of crystal deposit diseases require further study.
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