Genetic Deciphering of Early-Onset and Severe Retinal Dystrophy Associated with Sensorineural Hearing Loss.

Genetic Deciphering of Early-Onset and Severe Retinal Dystrophy Associated with Sensorineural Hearing Loss. Adv Exp Med Biol. 2019;1185:233-238 Authors: Mechaussier S, Marlin S, Kaplan J, Rozet JM, Perrault I Abstract The specific association of Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (LCA-like) with sensorineural hearing loss (SHL) is uncommon. Recently, we ascribed some of these distinctive associations to dominant and de novo mutations in the β-tubulin 4B isotype-encoding gene (TUBB4B), providing a link between a sensorineural disease and anomalies in microtubules behavior. Here, we report 12 sporadic cases with LCA/SHL or LCA-like/SHL and no TUBB4B mutation. Trio-based whole exome sequencing (WES) identified disease-causing mutations in 5/12 cases. Four out of five carried biallelic mutations in PEX1 (1/4) or PEX6 (3/4), involved in peroxisome biogenesis disorders from Zellweger syndrome characterized by severe neurologic and neurosensory dysfunctions, craniofacial abnormalities, and liver dysfunction to Heimler syndrome associating SHL, enamel hypoplasia of the secondary dentition, nail abnormalities, and occasional retinal disease. Upon reexamination, the index case carrying PEX1 mutations, a 4-year-old girl, presented additional symptoms consistent with Zellweger syndrome. Reexamination of individuals with PEX6 mutations (1/3 unavailable) revealed normal nails but enamel hypoplasia affecting o...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research