Cargando…
Compound Phenotype Due to Recessive Variants in LARP7 and OTOG Genes Disclosed by an Integrated Approach of SNP-Array and Whole Exome Sequencing
Neurodevelopmental disorders are a challenge in medical genetics due to genetic heterogeneity and complex genotype-phenotype correlations. For this reason, the resolution of single cases not belonging to well-defined syndromes often requires an integrated approach of multiple whole-genome technologi...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230222/ https://www.ncbi.nlm.nih.gov/pubmed/32244554 http://dx.doi.org/10.3390/genes11040379 |
_version_ | 1783534899232243712 |
---|---|
author | Palumbo, Pietro Palumbo, Orazio Leone, Maria Pia di Muro, Ester Castellana, Stefano Bisceglia, Luigi Mazza, Tommaso Carella, Massimo Castori, Marco |
author_facet | Palumbo, Pietro Palumbo, Orazio Leone, Maria Pia di Muro, Ester Castellana, Stefano Bisceglia, Luigi Mazza, Tommaso Carella, Massimo Castori, Marco |
author_sort | Palumbo, Pietro |
collection | PubMed |
description | Neurodevelopmental disorders are a challenge in medical genetics due to genetic heterogeneity and complex genotype-phenotype correlations. For this reason, the resolution of single cases not belonging to well-defined syndromes often requires an integrated approach of multiple whole-genome technologies. Such an approach has also unexpectedly revealed a complex molecular basis in an increasing number of patients, for whom the original suspect of a pleiotropic syndrome has been resolved as the summation effect of multiple genes. We describe a 10-year-old boy, the third son of first-cousin parents, with global developmental delay, facial dysmorphism, and bilateral deafness. SNP-array analysis revealed regions of homozygosity (ROHs) in multiple chromosome regions. Whole-exome sequencing prioritized on gene-mapping into the ROHs showed homozygosity for the likely pathogenic c.1097_1098delAG p. (Arg366Thrfs*2) frameshift substitution in LARP7 and the likely pathogenic c.5743C>T p.(Arg1915*) nonsense variant in OTOG. Recessive variants in LARP7 cause Alazami syndrome, while variants in OTOG cause an extremely rare autosomal recessive form of neurosensorial deafness. Previously unreported features were acrocyanosis and palmoplantar hyperhidrosis. This case highlights the utility of encouraging technological updates in medical genetics laboratories involved in the study of neurodevelopmental disorders and integrating laboratory outputs with the competencies of next-generation clinicians. |
format | Online Article Text |
id | pubmed-7230222 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72302222020-05-28 Compound Phenotype Due to Recessive Variants in LARP7 and OTOG Genes Disclosed by an Integrated Approach of SNP-Array and Whole Exome Sequencing Palumbo, Pietro Palumbo, Orazio Leone, Maria Pia di Muro, Ester Castellana, Stefano Bisceglia, Luigi Mazza, Tommaso Carella, Massimo Castori, Marco Genes (Basel) Article Neurodevelopmental disorders are a challenge in medical genetics due to genetic heterogeneity and complex genotype-phenotype correlations. For this reason, the resolution of single cases not belonging to well-defined syndromes often requires an integrated approach of multiple whole-genome technologies. Such an approach has also unexpectedly revealed a complex molecular basis in an increasing number of patients, for whom the original suspect of a pleiotropic syndrome has been resolved as the summation effect of multiple genes. We describe a 10-year-old boy, the third son of first-cousin parents, with global developmental delay, facial dysmorphism, and bilateral deafness. SNP-array analysis revealed regions of homozygosity (ROHs) in multiple chromosome regions. Whole-exome sequencing prioritized on gene-mapping into the ROHs showed homozygosity for the likely pathogenic c.1097_1098delAG p. (Arg366Thrfs*2) frameshift substitution in LARP7 and the likely pathogenic c.5743C>T p.(Arg1915*) nonsense variant in OTOG. Recessive variants in LARP7 cause Alazami syndrome, while variants in OTOG cause an extremely rare autosomal recessive form of neurosensorial deafness. Previously unreported features were acrocyanosis and palmoplantar hyperhidrosis. This case highlights the utility of encouraging technological updates in medical genetics laboratories involved in the study of neurodevelopmental disorders and integrating laboratory outputs with the competencies of next-generation clinicians. MDPI 2020-03-31 /pmc/articles/PMC7230222/ /pubmed/32244554 http://dx.doi.org/10.3390/genes11040379 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Palumbo, Pietro Palumbo, Orazio Leone, Maria Pia di Muro, Ester Castellana, Stefano Bisceglia, Luigi Mazza, Tommaso Carella, Massimo Castori, Marco Compound Phenotype Due to Recessive Variants in LARP7 and OTOG Genes Disclosed by an Integrated Approach of SNP-Array and Whole Exome Sequencing |
title | Compound Phenotype Due to Recessive Variants in LARP7 and OTOG Genes Disclosed by an Integrated Approach of SNP-Array and Whole Exome Sequencing |
title_full | Compound Phenotype Due to Recessive Variants in LARP7 and OTOG Genes Disclosed by an Integrated Approach of SNP-Array and Whole Exome Sequencing |
title_fullStr | Compound Phenotype Due to Recessive Variants in LARP7 and OTOG Genes Disclosed by an Integrated Approach of SNP-Array and Whole Exome Sequencing |
title_full_unstemmed | Compound Phenotype Due to Recessive Variants in LARP7 and OTOG Genes Disclosed by an Integrated Approach of SNP-Array and Whole Exome Sequencing |
title_short | Compound Phenotype Due to Recessive Variants in LARP7 and OTOG Genes Disclosed by an Integrated Approach of SNP-Array and Whole Exome Sequencing |
title_sort | compound phenotype due to recessive variants in larp7 and otog genes disclosed by an integrated approach of snp-array and whole exome sequencing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230222/ https://www.ncbi.nlm.nih.gov/pubmed/32244554 http://dx.doi.org/10.3390/genes11040379 |
work_keys_str_mv | AT palumbopietro compoundphenotypeduetorecessivevariantsinlarp7andotoggenesdisclosedbyanintegratedapproachofsnparrayandwholeexomesequencing AT palumboorazio compoundphenotypeduetorecessivevariantsinlarp7andotoggenesdisclosedbyanintegratedapproachofsnparrayandwholeexomesequencing AT leonemariapia compoundphenotypeduetorecessivevariantsinlarp7andotoggenesdisclosedbyanintegratedapproachofsnparrayandwholeexomesequencing AT dimuroester compoundphenotypeduetorecessivevariantsinlarp7andotoggenesdisclosedbyanintegratedapproachofsnparrayandwholeexomesequencing AT castellanastefano compoundphenotypeduetorecessivevariantsinlarp7andotoggenesdisclosedbyanintegratedapproachofsnparrayandwholeexomesequencing AT bisceglialuigi compoundphenotypeduetorecessivevariantsinlarp7andotoggenesdisclosedbyanintegratedapproachofsnparrayandwholeexomesequencing AT mazzatommaso compoundphenotypeduetorecessivevariantsinlarp7andotoggenesdisclosedbyanintegratedapproachofsnparrayandwholeexomesequencing AT carellamassimo compoundphenotypeduetorecessivevariantsinlarp7andotoggenesdisclosedbyanintegratedapproachofsnparrayandwholeexomesequencing AT castorimarco compoundphenotypeduetorecessivevariantsinlarp7andotoggenesdisclosedbyanintegratedapproachofsnparrayandwholeexomesequencing |