Case Report: Identification of likely recurrent CEP290 mutation in a child with Joubert syndrome and cerebello-retinal-renal features.

Autor:	Spahiu L; Pediatric Clinic, University Clinical Center of Kosovo, Prishtina, Kosovo (Serbia and Montenegro)., Sayer JA; Newcastle Biomedical Research Centre, NIHR, Newcastle upon Tyne, Tyne and Wear, UK.; Renal Services, Newcastle upon Tyne Hospitals National Health Service Foundation Trust, Newcastle, Tyne and Wear, NE7 7DN, UK.; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, Tyne and Wear, NE1 3BZ, UK., Behluli E; Pediatric Clinic, University Clinical Center of Kosovo, Prishtina, Kosovo (Serbia and Montenegro)., Liehr T; Institute of Human Genetics, Jena University Hospital, Jena, D-07747, Germany., Temaj G; Faculty of Pharmacy, College UBT, Prishtina, Kosovo (Serbia and Montenegro).
Jazyk:	angličtina
Zdroj:	F1000Research [F1000Res] 2023 Mar 31; Vol. 11, pp. 388. Date of Electronic Publication: 2023 Mar 31 (Print Publication: 2022).
DOI:	10.12688/f1000research.109628.2
Abstrakt:	Background. Joubert syndrome (JS) is a rare autosomal recessive ciliopathy with an estimated prevalence of 1 in 100,000. JS is characterized by hyperpnoea, hypotonia, ataxia, developmental delay and various neuropathological abnormalities in the brain including cerebellar hypoplasia and cerebellar vermis aplasia. JS can also have variable multi-organ involvement, including the retina, kidneys, liver, and musculoskeletal system. Methods and Results . Here we report a clinical description of two-year-old girl presenting with breathing difficulties, hyperechoic kidneys with loss of corticomedullary differentiation. Brain magnetic resonance imaging revealed the typical molar tooth sign consistent with a clinical diagnosis of JS and retinal examination showed severe retinal dystrophy leading to blindness. Molecular genetic analysis using whole exome sequencing and Sanger sequence confirmation demonstrated a homozygous mutation (c.5493delA, p.(A1832fs*19) in CEP290 which segregated from either parent and was consistent with the multisystem ciliopathy phenotype. This precise variant has been described previously in 2 families from the Kosovar-Albanian region suggesting this allele is a recurrent mutation in this population. Conclusions. Mutations in CEP290 lead to multisystem ciliopathy syndromes and molecular genetic diagnostics of such cases allows precise diagnosis, screening of at risk relatives and appropriate management. Competing Interests: No competing interests were disclosed. (Copyright: © 2023 Spahiu L et al.)
Databáze:	MEDLINE
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