Faculty Opinions recommendation of Somatic USP8 gene mutations are a common cause of pediatric cushing disease.

AbstractRhodopsin (RHO) gene mutations are a common cause of autosomal dominant retinitis pigmentosa (ADRP). The need to suppress toxic protein expression together with mutational heterogeneity pose challenges for treatment development. Mirtrons are atypical RNA interference effectors that are spliced from transcripts as short introns. Here, we develop a novel mirtron-based knockdown/replacement gene therapy for the mutation-independent treatment of RHO-related ADRP, and demonstrate efficacy in a relevant mammalian model. Splicing and potency of rhodopsin-targeting candidate mirtrons are initially determined, and a mirtron-resistant codon-modified version of the rhodopsin coding sequence is validated in vitro. These elements are then combined within a single adeno-associated virus (AAV) and delivered subretinally in a RhoP23H knock-in mouse model of ADRP. This results in significant mouse-to-human rhodopsin RNA replacement and is associated with a slowing of retinal degeneration. This provides proof of principle that synthetic mirtrons delivered by AAV are capable of reducing disease severity in vivo.

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Exclusion of growth factor gene mutations as a common cause of Sotos syndrome

American Journal of Medical Genetics ◽

10.1002/1096-8628(20010101)98:1<101::aid-ajmg1016>3.0.co;2-p ◽

2000 ◽

Vol 98 (1) ◽

pp. 101-102 ◽

Cited By ~ 2

Author(s):

Angela E. Lin ◽

Qing Liu ◽

Glenn B. Mannheim ◽

Basil T. Darras

Keyword(s):

Growth Factor ◽

Gene Mutations ◽

Sotos Syndrome ◽

Common Cause ◽

Factor Gene ◽

Growth Factor Gene

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Spectrum and Frequency of the GJB2 Gene Mutations Among Latvian Patients with Prelingual Nonsyndromic Hearing Loss

Proceedings of the Latvian Academy of Sciences Section B Natural Exact and Applied Sciences ◽

10.2478/v10046-009-0031-8 ◽

2009 ◽

Vol 63 (4-5) ◽

pp. 198-203

Author(s):

Olga Šterna ◽

Natālija Proņina ◽

Ieva Grīnfelde ◽

Sandra Kušķe ◽

Astrīda Krūmiņa ◽

...

Keyword(s):

Hearing Loss ◽

Gene Mutations ◽

Gjb2 Gene ◽

Connexin 26 ◽

Compound Heterozygous ◽

Nonsyndromic Hearing Loss ◽

Profound Hearing Loss ◽

Common Cause ◽

Gjb2 Mutation ◽

35Delg Mutation

Spectrum and Frequency of the GJB2 Gene Mutations Among Latvian Patients with Prelingual Nonsyndromic Hearing Loss Mutations in the GJB2 gene (connexin 26) are the most common cause of congenital nonsyndromic severe-to-profound hearing loss. Sixty-five hearing impaired probands from Latvia were tested for mutations in the GJB2 gene to determine the percentage of hearing loss attributed to connexin 26 and the types of mutations in this population. A total of 62% of patients tested had GJB2 mutations. Four different mutations in the GJB2 gene were identified in Latvian patients with nonsyndromic sensorineural hearing loss: 35delG, 311-324del14, 235delC and M34T. The most prevalent mutation is 35delG (47% of all probands were homozygous and 8% compound heterozygous). Our findings support the conclusion that the 35delG mutation is the most prevalent GJB2 mutation and that it is the common cause of hereditary nonsyndromic hearing loss in populations of European descent.

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