John Libbey Eurotext

OCLN gene variants identified in three patients with severe neurodevelopmental disorder associated with epilepsy, intellectual disability and malformation of cortical development Volume 23, numéro 6, December 2021

Illustrations

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Tableaux

Auteurs
1 Department of Medical Biology and Genetics, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
2 Department of Pediatric Neurology, Dr. Behcet Uz Children's Hospital, Izmir, Turkey
3 Department of Pediatrics, Division of Child Neurology, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
* Correspondence: Sultan Cingoz Department of Medical Biology and Genetics, Faculty of Medicine Dokuz Eylul University 35340 Inciralti, Izmir, Turkey

Objective

Homozygous OCLN variants have been reported in patients with band-like calcification with simplified gyration and polymicrogyria (BLC-PMG) which is characterized by microcephaly, intracranial calcification and severe developmental delay. The OCLN gene encodes the integral membrane protein, occludin.

Methods

Herein, we report three additional cases with homozygous OCLN variants that were identified via Trio-WES in two consanguineous unrelated families.

Results

We detected a previously reported frameshift variant in two cases in Family 1 and a novel missense variant in a case in Family 2. The potential pathogenicity of both variants in the index cases was investigated using in silico tools, and both variants were determined to be rare and predicted to be pathogenic. All of the presented cases exhibited clinical features in common with earlier reported patients, such as severe intellectual disability, microcephaly, polymicrogyria, epilepsy, hypotonia and severe developmental delay. On the other hand, in addition to the common phenotypic features, our two cases in Family 1 showed features similar to those previously reported in cases from two Turkish families carrying the same frameshift variant, such as renal failure.

Significance

We herein expand the spectrum of OCLN gene variants with a description of an additional novel homozygous missense variant. The frameshift variant in Turkish cases may thus be a phenotype associated with renal failure in addition to the core phenotype associated with other OCLN gene variants, and such variants could be important for rapid molecular diagnosis and treatment. The frameshift variant in Turkish cases might also be investigated for both a potential founder effect and mutational hot spot.