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

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 J...

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Bibliographic Details
Published in:Clinical genetics 2023-04, Vol.103 (4), p.448-452
Main Authors: Martínez‐Granero, Francisco, Martínez‐Cayuelas, Elena, Rodilla, Cristina, Núñez‐Moreno, Gonzalo, Rodríguez de Alba, Marta, Blanco‐Kelly, Fiona, Romero, Raquel, Minguez, Pablo, Ayuso, Carmen, Lorda‐Sanchez, Isabel, Corton, Marta, Almoguera, Berta
Format: Article
Language:English
Subjects:
Abnormalities, Multiple - genetics
Brain
Breakpoints
Case reports
Cerebellum
Congenital defects
Copy number
CPLANE1
developmental delay
Exons
Eye Abnormalities - genetics
Genetic disorders
Humans
intragenic duplication
Joubert syndrome
Kidney Diseases, Cystic - diagnosis
long‐read sequencing
Neurodevelopmental disorders
Retina - pathology
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Summary: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.
ISSN:0009-9163
1399-0004
DOI:10.1111/cge.14306