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Identification of a Novel Variant in Myelin Regulatory Growth Factor by Next-Generation Sequencing Led to the Detection of a Clinically Inapparent Congenital Heart Defect in a Patient with a 46,XY Disorder of Sex Development

In patients with 46,XY disorders of sex development (DSDs), next-generation sequencing (NGS) has high diagnostic efficiency. One contribution to this diagnostic approach is the possibility of applying reverse phenotyping when a variant in a gene associated with multiple organ hits is found. Our aim...

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Autores principales: Correa Brito, Lourdes, Grinspon, Romina P., Lopez Dacal, Jimena, Scaglia, Paula, Esnaola Azcoiti, María, Izquierdo, Agustín, Ropelato, María Gabriela, Rey, Rodolfo A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381246/
https://www.ncbi.nlm.nih.gov/pubmed/37511771
http://dx.doi.org/10.3390/jpm13071158
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author Correa Brito, Lourdes
Grinspon, Romina P.
Lopez Dacal, Jimena
Scaglia, Paula
Esnaola Azcoiti, María
Izquierdo, Agustín
Ropelato, María Gabriela
Rey, Rodolfo A.
author_facet Correa Brito, Lourdes
Grinspon, Romina P.
Lopez Dacal, Jimena
Scaglia, Paula
Esnaola Azcoiti, María
Izquierdo, Agustín
Ropelato, María Gabriela
Rey, Rodolfo A.
author_sort Correa Brito, Lourdes
collection PubMed
description In patients with 46,XY disorders of sex development (DSDs), next-generation sequencing (NGS) has high diagnostic efficiency. One contribution to this diagnostic approach is the possibility of applying reverse phenotyping when a variant in a gene associated with multiple organ hits is found. Our aim is to report a case of a patient with 46,XY DSDs in whom the identification of a novel variant in MYRF led to the detection of a clinically inapparent congenital heart defect. A full-term newborn presented with ambiguous genitalia, as follows: a 2 cm phallus, penoscrotal hypospadias, partially fused labioscrotal folds, an anogenital distance of 1.2 cm, and non-palpable gonads. The karyotype was 46,XY, serum testosterone and AMH were low, whereas LH and FSH were high, leading to the diagnosis of dysgenetic DSD. Whole exome sequencing identified a novel, heterozygous, nonsense variant in MYRF, classified as pathogenic according to the ACMG criteria. MYRF encodes a membrane-bound transcriptional factor expressed in several tissues associated with OCUGS syndrome (ophthalmic, cardiac, and urogenital anomalies). In the patient, oriented clinical assessment ruled out ophthalmic defects, but ultrasonography confirmed meso/dextrocardia. We report a novel MYRF variant in a patient with 46,XY DSDs, allowing us to identify a clinically inapparent congenital heart defect by reverse phenotyping.
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spelling pubmed-103812462023-07-29 Identification of a Novel Variant in Myelin Regulatory Growth Factor by Next-Generation Sequencing Led to the Detection of a Clinically Inapparent Congenital Heart Defect in a Patient with a 46,XY Disorder of Sex Development Correa Brito, Lourdes Grinspon, Romina P. Lopez Dacal, Jimena Scaglia, Paula Esnaola Azcoiti, María Izquierdo, Agustín Ropelato, María Gabriela Rey, Rodolfo A. J Pers Med Case Report In patients with 46,XY disorders of sex development (DSDs), next-generation sequencing (NGS) has high diagnostic efficiency. One contribution to this diagnostic approach is the possibility of applying reverse phenotyping when a variant in a gene associated with multiple organ hits is found. Our aim is to report a case of a patient with 46,XY DSDs in whom the identification of a novel variant in MYRF led to the detection of a clinically inapparent congenital heart defect. A full-term newborn presented with ambiguous genitalia, as follows: a 2 cm phallus, penoscrotal hypospadias, partially fused labioscrotal folds, an anogenital distance of 1.2 cm, and non-palpable gonads. The karyotype was 46,XY, serum testosterone and AMH were low, whereas LH and FSH were high, leading to the diagnosis of dysgenetic DSD. Whole exome sequencing identified a novel, heterozygous, nonsense variant in MYRF, classified as pathogenic according to the ACMG criteria. MYRF encodes a membrane-bound transcriptional factor expressed in several tissues associated with OCUGS syndrome (ophthalmic, cardiac, and urogenital anomalies). In the patient, oriented clinical assessment ruled out ophthalmic defects, but ultrasonography confirmed meso/dextrocardia. We report a novel MYRF variant in a patient with 46,XY DSDs, allowing us to identify a clinically inapparent congenital heart defect by reverse phenotyping. MDPI 2023-07-19 /pmc/articles/PMC10381246/ /pubmed/37511771 http://dx.doi.org/10.3390/jpm13071158 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 Case Report
Correa Brito, Lourdes
Grinspon, Romina P.
Lopez Dacal, Jimena
Scaglia, Paula
Esnaola Azcoiti, María
Izquierdo, Agustín
Ropelato, María Gabriela
Rey, Rodolfo A.
Identification of a Novel Variant in Myelin Regulatory Growth Factor by Next-Generation Sequencing Led to the Detection of a Clinically Inapparent Congenital Heart Defect in a Patient with a 46,XY Disorder of Sex Development
title Identification of a Novel Variant in Myelin Regulatory Growth Factor by Next-Generation Sequencing Led to the Detection of a Clinically Inapparent Congenital Heart Defect in a Patient with a 46,XY Disorder of Sex Development
title_full Identification of a Novel Variant in Myelin Regulatory Growth Factor by Next-Generation Sequencing Led to the Detection of a Clinically Inapparent Congenital Heart Defect in a Patient with a 46,XY Disorder of Sex Development
title_fullStr Identification of a Novel Variant in Myelin Regulatory Growth Factor by Next-Generation Sequencing Led to the Detection of a Clinically Inapparent Congenital Heart Defect in a Patient with a 46,XY Disorder of Sex Development
title_full_unstemmed Identification of a Novel Variant in Myelin Regulatory Growth Factor by Next-Generation Sequencing Led to the Detection of a Clinically Inapparent Congenital Heart Defect in a Patient with a 46,XY Disorder of Sex Development
title_short Identification of a Novel Variant in Myelin Regulatory Growth Factor by Next-Generation Sequencing Led to the Detection of a Clinically Inapparent Congenital Heart Defect in a Patient with a 46,XY Disorder of Sex Development
title_sort identification of a novel variant in myelin regulatory growth factor by next-generation sequencing led to the detection of a clinically inapparent congenital heart defect in a patient with a 46,xy disorder of sex development
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381246/
https://www.ncbi.nlm.nih.gov/pubmed/37511771
http://dx.doi.org/10.3390/jpm13071158
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