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Complex Presentation of Hao-Fountain Syndrome Solved by Exome Sequencing Highlighting Co-Occurring Genomic Variants

Objective: The co-occurrence of pathogenic variants has emerged as a relatively common finding underlying complex phenotypes. Here, we used whole-exome sequencing (WES) to solve an unclassified multisystem clinical presentation. Patients and Methods: A 20-year-old woman affected by moderate intellec...

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Autores principales: Priolo, Manuela, Mancini, Cecilia, Pizzi, Simone, Chiriatti, Luigi, Radio, Francesca Clementina, Cordeddu, Viviana, Pintomalli, Letizia, Mammì, Corrado, Dallapiccola, Bruno, Tartaglia, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141324/
https://www.ncbi.nlm.nih.gov/pubmed/35627274
http://dx.doi.org/10.3390/genes13050889
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author Priolo, Manuela
Mancini, Cecilia
Pizzi, Simone
Chiriatti, Luigi
Radio, Francesca Clementina
Cordeddu, Viviana
Pintomalli, Letizia
Mammì, Corrado
Dallapiccola, Bruno
Tartaglia, Marco
author_facet Priolo, Manuela
Mancini, Cecilia
Pizzi, Simone
Chiriatti, Luigi
Radio, Francesca Clementina
Cordeddu, Viviana
Pintomalli, Letizia
Mammì, Corrado
Dallapiccola, Bruno
Tartaglia, Marco
author_sort Priolo, Manuela
collection PubMed
description Objective: The co-occurrence of pathogenic variants has emerged as a relatively common finding underlying complex phenotypes. Here, we used whole-exome sequencing (WES) to solve an unclassified multisystem clinical presentation. Patients and Methods: A 20-year-old woman affected by moderate intellectual disability (ID), dysmorphic features, hypertrichosis, scoliosis, recurrent bronchitis, and pneumonia with bronchiectasis, colelithiasis, chronic severe constipation, and a family history suggestive of autosomal dominant recurrence of polycystic kidney disease was analyzed by WES to identify the genomic events underlying the condition. Results: Four co-occurring genomic events fully explaining the proband’s clinical features were identified. A de novo truncating USP7 variant was disclosed as the cause of Hao–Fountain syndrome, a disorder characterized by syndromic ID and distinctive behavior. Compound heterozygosity for a major cystic fibrosis-causing variant and the modulator allele, IVS8-5T, in CFTR explained the recurrent upper and lower respiratory way infections, bronchiectasis, cholelithiasis, and chronic constipation. Finally, a truncating PKD2 variant co-segregating with polycystic kidney disease in the family allowed presymptomatic disease diagnosis. Conclusions: The co-occurring variants in USP7 and CFTR variants explained the multisystem disorder of the patient. The comprehensive dissection of the phenotype and early diagnosis of autosomal dominant polycystic kidney disease allowed us to manage the CFTR-related disorder symptoms and monitor renal function and other complications associated with PKD2 haploinsufficiency, addressing proper care and surveillance.
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spelling pubmed-91413242022-05-28 Complex Presentation of Hao-Fountain Syndrome Solved by Exome Sequencing Highlighting Co-Occurring Genomic Variants Priolo, Manuela Mancini, Cecilia Pizzi, Simone Chiriatti, Luigi Radio, Francesca Clementina Cordeddu, Viviana Pintomalli, Letizia Mammì, Corrado Dallapiccola, Bruno Tartaglia, Marco Genes (Basel) Article Objective: The co-occurrence of pathogenic variants has emerged as a relatively common finding underlying complex phenotypes. Here, we used whole-exome sequencing (WES) to solve an unclassified multisystem clinical presentation. Patients and Methods: A 20-year-old woman affected by moderate intellectual disability (ID), dysmorphic features, hypertrichosis, scoliosis, recurrent bronchitis, and pneumonia with bronchiectasis, colelithiasis, chronic severe constipation, and a family history suggestive of autosomal dominant recurrence of polycystic kidney disease was analyzed by WES to identify the genomic events underlying the condition. Results: Four co-occurring genomic events fully explaining the proband’s clinical features were identified. A de novo truncating USP7 variant was disclosed as the cause of Hao–Fountain syndrome, a disorder characterized by syndromic ID and distinctive behavior. Compound heterozygosity for a major cystic fibrosis-causing variant and the modulator allele, IVS8-5T, in CFTR explained the recurrent upper and lower respiratory way infections, bronchiectasis, cholelithiasis, and chronic constipation. Finally, a truncating PKD2 variant co-segregating with polycystic kidney disease in the family allowed presymptomatic disease diagnosis. Conclusions: The co-occurring variants in USP7 and CFTR variants explained the multisystem disorder of the patient. The comprehensive dissection of the phenotype and early diagnosis of autosomal dominant polycystic kidney disease allowed us to manage the CFTR-related disorder symptoms and monitor renal function and other complications associated with PKD2 haploinsufficiency, addressing proper care and surveillance. MDPI 2022-05-16 /pmc/articles/PMC9141324/ /pubmed/35627274 http://dx.doi.org/10.3390/genes13050889 Text en © 2022 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 Article
Priolo, Manuela
Mancini, Cecilia
Pizzi, Simone
Chiriatti, Luigi
Radio, Francesca Clementina
Cordeddu, Viviana
Pintomalli, Letizia
Mammì, Corrado
Dallapiccola, Bruno
Tartaglia, Marco
Complex Presentation of Hao-Fountain Syndrome Solved by Exome Sequencing Highlighting Co-Occurring Genomic Variants
title Complex Presentation of Hao-Fountain Syndrome Solved by Exome Sequencing Highlighting Co-Occurring Genomic Variants
title_full Complex Presentation of Hao-Fountain Syndrome Solved by Exome Sequencing Highlighting Co-Occurring Genomic Variants
title_fullStr Complex Presentation of Hao-Fountain Syndrome Solved by Exome Sequencing Highlighting Co-Occurring Genomic Variants
title_full_unstemmed Complex Presentation of Hao-Fountain Syndrome Solved by Exome Sequencing Highlighting Co-Occurring Genomic Variants
title_short Complex Presentation of Hao-Fountain Syndrome Solved by Exome Sequencing Highlighting Co-Occurring Genomic Variants
title_sort complex presentation of hao-fountain syndrome solved by exome sequencing highlighting co-occurring genomic variants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141324/
https://www.ncbi.nlm.nih.gov/pubmed/35627274
http://dx.doi.org/10.3390/genes13050889
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