High prevalence of syndromic hearing loss in Mexican children undergoing cochlear implantation.

Objective: Studies evaluating genetic sensorineural hearing loss (SNHL) in Hispanic and Latino populations using genomic technologies are lacking. Recent data has shown that Hispanic and Latino children display lower genetic diagnostic rates despite similar prevalence rates of SNHL to their Asian and White counterparts, thus negatively affecting their clinical care. Our objective was to determine the genetic contribution to SNHL in a population of Mexican children undergoing evaluation for cochlear implantation. Methods: Pediatric patients from Mexico with severe to profound SNHL undergoing evaluation for cochlear implantation were recruited. Exome sequencing (ES) or hearing loss gene panel testing was performed. Variant pathogenicity was established in accordance to criteria established by the American College of Medical Genetics, and variants of interest were clinically confirmed via CLIA certified laboratory. Results: Genetic evaluation was completed for 30 Mexican children with severe to profound SNHL. A genetic cause was identified for 47% (14) of probands, and 7% (2) probands had an inconclusive result. Of the diagnoses, 10 (71%) were syndromic or likely syndromic, and 4 (29%) were nonsyndromic. Eight probands (80% of all syndromic diagnoses) were diagnosed with a syndromic form of hearing loss that mimics a nonsyndromic clinical presentation at a young age and so could not be suspected based on clinical evaluation alone without genetic testing. Conclusion: This is the largest study to date to use comprehensive genomic testing for the evaluation of Mexican children with severe to profound SNHL. A significant proportion of children in this cohort were diagnosed with syndromic hearing loss. Future study in a larger cohort of Mexican children with varying degrees of hearing loss is required to improve the efficacy of genetic testing and timely medical intervention within these ethnically diverse populations. Level of evidence: Level 4 (cohort study).

Corrigendum: ALG1-CDG Caused by Non-Functional Alternative Splicing Involving a Novel Pathogenic Complex Allele.

[This corrects the article DOI: 10.3389/fgene.2021.744884.].

ALG1-CDG Caused by Non-functional Alternative Splicing Involving a Novel Pathogenic Complex Allele.

This study reports on a Mexican mestizo patient with a multi-systemic syndrome including neurological involvement and a type I serum transferrin profile. Clinical exome sequencing revealed complex alleles in ALG1, the encoding gene for the chitobiosyldiphosphodolichol beta-mannosyltransferase that participates in the formation of the dolichol-pyrophosphate-GlcNAc2Man5, a lipid-linked glycan intermediate during N-glycan synthesis. The identified complex alleles were NM_019109.5(ALG1): c.[208 + 16_208 + 19dup; 208 + 25G > T] and NM_019109.5(ALG1): c.[208 + 16_208 + 19dup; 1312C > T]. Although both alleles carried the benign variant c.208 + 16_208 + 19dup, one allele carried a known ALG1 pathogenic variant (c.1312C > T), while the other carried a new uncharacterized variant (c.208 + 25G > T) causing non-functional alternative splicing that, in conjunction with the benign variant, defines the pathogenic protein effect (p.N70S_S71ins9). The presence in the patient's serum of the pathognomonic N-linked mannose-deprived tetrasaccharide marker for ALG1-CDG (Neu5Acα2,6Galß1,4-GlcNAcß1,4GlcNAc) further supported this diagnosis. This is the first report of an ALG1-CDG patient from Latin America.