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Rare IFT140-Associated Phenotype of Cranioectodermal Dysplasia and Features of Diagnostic Journey in Patients with Suspected Ciliopathies

Here we present a patient with a cranioectodermal phenotype associated with pathogenic variants in the IFT140 gene. Most frequently, pathogenic variants in IFT140 correspond to the phenotype of Mainzer–Saldino syndrome. Only four patients have previously been described with this cranioectodermal phe...

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Autores principales: Sharova, Margarita, Markova, Tatyana, Sumina, Maria, Petukhova, Marina, Bulakh, Maria, Ryzhkova, Oxana, Nagornova, Tatyana, Ionova, Sofya, Marakhonov, Andrey, Dadali, Elena, Kutsev, Sergey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454909/
https://www.ncbi.nlm.nih.gov/pubmed/37628605
http://dx.doi.org/10.3390/genes14081553
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author Sharova, Margarita
Markova, Tatyana
Sumina, Maria
Petukhova, Marina
Bulakh, Maria
Ryzhkova, Oxana
Nagornova, Tatyana
Ionova, Sofya
Marakhonov, Andrey
Dadali, Elena
Kutsev, Sergey
author_facet Sharova, Margarita
Markova, Tatyana
Sumina, Maria
Petukhova, Marina
Bulakh, Maria
Ryzhkova, Oxana
Nagornova, Tatyana
Ionova, Sofya
Marakhonov, Andrey
Dadali, Elena
Kutsev, Sergey
author_sort Sharova, Margarita
collection PubMed
description Here we present a patient with a cranioectodermal phenotype associated with pathogenic variants in the IFT140 gene. Most frequently, pathogenic variants in IFT140 correspond to the phenotype of Mainzer–Saldino syndrome. Only four patients have previously been described with this cranioectodermal phenotype and variants in IFT140. In comparison to other IFT140-cranioectodermal patients, our proband had similar skeletal features among with early onset end-stage renal failure that required kidney transplantation but did not have common ophthalmological features such as retinopathy, optic nerve atrophy, or nystagmus. Following exome sequencing, a splicing variant and exons 27–30 tandem duplication were suspected and further validated. The two other patients with Mainzer–Saldino syndrome that we described displayed a typical clinical picture but a special diagnostic journey. In both cases, at first only one pathogenic variant was detected following panel or exome NGS sequencing. Further WGS was performed for one of them where tandem duplication was found. Screening the third patient for the same tandem duplication was successful and revealed the presence of this duplication. Thus, we suggest that the description of the clinical feature polymorphism in a rare IFT140-cranioectodermal phenotype is extremely important for providing genetic counseling for families, as well as the formation of the correct diagnostic path for patients with a variant in IFT140.
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spelling pubmed-104549092023-08-26 Rare IFT140-Associated Phenotype of Cranioectodermal Dysplasia and Features of Diagnostic Journey in Patients with Suspected Ciliopathies Sharova, Margarita Markova, Tatyana Sumina, Maria Petukhova, Marina Bulakh, Maria Ryzhkova, Oxana Nagornova, Tatyana Ionova, Sofya Marakhonov, Andrey Dadali, Elena Kutsev, Sergey Genes (Basel) Brief Report Here we present a patient with a cranioectodermal phenotype associated with pathogenic variants in the IFT140 gene. Most frequently, pathogenic variants in IFT140 correspond to the phenotype of Mainzer–Saldino syndrome. Only four patients have previously been described with this cranioectodermal phenotype and variants in IFT140. In comparison to other IFT140-cranioectodermal patients, our proband had similar skeletal features among with early onset end-stage renal failure that required kidney transplantation but did not have common ophthalmological features such as retinopathy, optic nerve atrophy, or nystagmus. Following exome sequencing, a splicing variant and exons 27–30 tandem duplication were suspected and further validated. The two other patients with Mainzer–Saldino syndrome that we described displayed a typical clinical picture but a special diagnostic journey. In both cases, at first only one pathogenic variant was detected following panel or exome NGS sequencing. Further WGS was performed for one of them where tandem duplication was found. Screening the third patient for the same tandem duplication was successful and revealed the presence of this duplication. Thus, we suggest that the description of the clinical feature polymorphism in a rare IFT140-cranioectodermal phenotype is extremely important for providing genetic counseling for families, as well as the formation of the correct diagnostic path for patients with a variant in IFT140. MDPI 2023-07-28 /pmc/articles/PMC10454909/ /pubmed/37628605 http://dx.doi.org/10.3390/genes14081553 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Sharova, Margarita
Markova, Tatyana
Sumina, Maria
Petukhova, Marina
Bulakh, Maria
Ryzhkova, Oxana
Nagornova, Tatyana
Ionova, Sofya
Marakhonov, Andrey
Dadali, Elena
Kutsev, Sergey
Rare IFT140-Associated Phenotype of Cranioectodermal Dysplasia and Features of Diagnostic Journey in Patients with Suspected Ciliopathies
title Rare IFT140-Associated Phenotype of Cranioectodermal Dysplasia and Features of Diagnostic Journey in Patients with Suspected Ciliopathies
title_full Rare IFT140-Associated Phenotype of Cranioectodermal Dysplasia and Features of Diagnostic Journey in Patients with Suspected Ciliopathies
title_fullStr Rare IFT140-Associated Phenotype of Cranioectodermal Dysplasia and Features of Diagnostic Journey in Patients with Suspected Ciliopathies
title_full_unstemmed Rare IFT140-Associated Phenotype of Cranioectodermal Dysplasia and Features of Diagnostic Journey in Patients with Suspected Ciliopathies
title_short Rare IFT140-Associated Phenotype of Cranioectodermal Dysplasia and Features of Diagnostic Journey in Patients with Suspected Ciliopathies
title_sort rare ift140-associated phenotype of cranioectodermal dysplasia and features of diagnostic journey in patients with suspected ciliopathies
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454909/
https://www.ncbi.nlm.nih.gov/pubmed/37628605
http://dx.doi.org/10.3390/genes14081553
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