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Case Reports
. 2023 Apr;103(4):448-452.
doi: 10.1111/cge.14306. Epub 2023 Feb 8.

Biallelic intragenic tandem duplication of CPLANE1 in Joubert syndrome: A case report

Francisco Martínez-Granero  1 , Elena Martínez-Cayuelas  2 , Cristina Rodilla  1   3 , Gonzalo Núñez-Moreno  1   3   4 , Marta Rodríguez de Alba  1   3 , Fiona Blanco-Kelly  1   3 , Raquel Romero  1   3   4 , Pablo Minguez  1   3   4 , Carmen Ayuso  1   3 , Isabel Lorda-Sanchez  1   3 , Marta Corton  1   3 , Berta Almoguera  1   3
Affiliations
Case Reports

Biallelic intragenic tandem duplication of CPLANE1 in Joubert syndrome: A case report

Francisco Martínez-Granero et al. Clin Genet. 2023 Apr.

Abstract

Joubert syndrome (JS) is a clinically and genetically heterogeneous genetic disorder. To date, 40 JS-causing genes have been reported and CPLANE1 is one of the most frequently mutated, with biallelic pathogenic missense and truncating variants explaining up to 14% of JS cases. We present a case of JS diagnosed after the identification of a novel biallelic intragenic duplication of exons 20-46 of CPLANE1. The quadruplication was identified by short-read sequencing and copy number variant analysis and confirmed in tandem by long PCR with the breakpoints defined by a nanopore-based long-read sequencing approach. Based on the genetic findings and the clinical presentation of the patient, a brain MRI was ordered, evidencing the molar tooth sign, which confirmed the diagnosis of JS in the patient. This is, to the best of our knowledge, the first report of an intragenic duplication in this gene as the potential molecular mechanism of JS.

Keywords: CPLANE1; Joubert syndrome; developmental delay; intragenic duplication; long-read sequencing.

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References

REFERENCES

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