Sacha Laurent, Anne Vannier, Corinne Gehrig, Marc Abramowicz, Ariane Paoloni-Giacobino, Hélène Cao Van, Michel Guipponi
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引用次数: 0
Abstract
Biallelic loss-of-function variants in STRC contribute to mild-moderate hearing loss (DFNB16). Here, we report a female patient with mild hearing loss. Exome sequencing and MLPA analysis revealed STRC biallelic inactivation due to a nonsense and a CKMT1B-STRC deletion. Analysis of the self-reported normal-hearing parents revealed inconsistent Mendelian inheritance. Indeed, the mother was a heterozygous carrier of a CKTM1B-STRC-CATSPER2 deletion, and the father shared the same genotype as his daughter. He was later found to also have mild-moderate hearing loss. To address these discrepancies, we used long-read sequencing and optical genome mapping. We demonstrated that the father, in fact, carried a CKMT1B-STRC-CATSPER2 deletion in trans with the STRC nonsense variant and a tandem duplication of CATSPER2-CKMT1A. The proband inherited this latter haplotype, together with the maternal CKMT1B-STRC-CATSPER2 deletion. Combining these two technologies allowed us to fully elucidate the complex structural rearrangements at the STRC locus and provide appropriate genetic counselling.
期刊介绍:
The European Journal of Medical Genetics (EJMG) is a peer-reviewed journal that publishes articles in English on various aspects of human and medical genetics and of the genetics of experimental models.
Original clinical and experimental research articles, short clinical reports, review articles and letters to the editor are welcome on topics such as :
• Dysmorphology and syndrome delineation
• Molecular genetics and molecular cytogenetics of inherited disorders
• Clinical applications of genomics and nextgen sequencing technologies
• Syndromal cancer genetics
• Behavioral genetics
• Community genetics
• Fetal pathology and prenatal diagnosis
• Genetic counseling.