Case Report: Identification of likely recurrent CEP290 mutation in a child with Joubert syndrome and cerebello-retinal-renal features. [version 2; peer review: 2 approved]
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 v...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2023-03-01
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| Online Access: | https://f1000research.com/articles/11-388/v2 |
| _version_ | 1797823849782312960 |
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| author | Gazmend Temaj John A Sayer Lidvana Spahiu Thomas Liehr Emir Behluli |
| author_facet | Gazmend Temaj John A Sayer Lidvana Spahiu Thomas Liehr Emir Behluli |
| author_sort | Gazmend Temaj |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T10:30:06Z |
| format | Article |
| id | doaj.art-8d747da280bc493dbd61faa05b47dba0 |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-03-13T10:30:06Z |
| publishDate | 2023-03-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-8d747da280bc493dbd61faa05b47dba02023-05-19T00:00:00ZengF1000 Research LtdF1000Research2046-14022023-03-0111145997Case Report: Identification of likely recurrent CEP290 mutation in a child with Joubert syndrome and cerebello-retinal-renal features. [version 2; peer review: 2 approved]Gazmend Temaj0https://orcid.org/0000-0003-4807-2938John A Sayer1https://orcid.org/0000-0003-1881-3782Lidvana Spahiu2Thomas Liehr3https://orcid.org/0000-0003-1672-3054Emir Behluli4Faculty of Pharmacy, College UBT, Prishtina, Kosovo (Serbia and Montenegro)Newcastle Biomedical Research Centre, NIHR, Newcastle upon Tyne, Tyne and Wear, UKPediatric Clinic, University Clinical Center of Kosovo, Prishtina, Kosovo (Serbia and Montenegro)Institute of Human Genetics, Jena University Hospital, Jena, D-07747, GermanyPediatric Clinic, University Clinical Center of Kosovo, Prishtina, Kosovo (Serbia and Montenegro)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.https://f1000research.com/articles/11-388/v2Joubert syndrome CEP290 molecular genetics ciliopathy retinal dystrophyeng |
| spellingShingle | Gazmend Temaj John A Sayer Lidvana Spahiu Thomas Liehr Emir Behluli Case Report: Identification of likely recurrent CEP290 mutation in a child with Joubert syndrome and cerebello-retinal-renal features. [version 2; peer review: 2 approved] F1000Research Joubert syndrome CEP290 molecular genetics ciliopathy retinal dystrophy eng |
| title | Case Report: Identification of likely recurrent CEP290 mutation in a child with Joubert syndrome and cerebello-retinal-renal features. [version 2; peer review: 2 approved] |
| title_full | Case Report: Identification of likely recurrent CEP290 mutation in a child with Joubert syndrome and cerebello-retinal-renal features. [version 2; peer review: 2 approved] |
| title_fullStr | Case Report: Identification of likely recurrent CEP290 mutation in a child with Joubert syndrome and cerebello-retinal-renal features. [version 2; peer review: 2 approved] |
| title_full_unstemmed | Case Report: Identification of likely recurrent CEP290 mutation in a child with Joubert syndrome and cerebello-retinal-renal features. [version 2; peer review: 2 approved] |
| title_short | Case Report: Identification of likely recurrent CEP290 mutation in a child with Joubert syndrome and cerebello-retinal-renal features. [version 2; peer review: 2 approved] |
| title_sort | case report identification of likely recurrent cep290 mutation in a child with joubert syndrome and cerebello retinal renal features version 2 peer review 2 approved |
| topic | Joubert syndrome CEP290 molecular genetics ciliopathy retinal dystrophy eng |
| url | https://f1000research.com/articles/11-388/v2 |
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