DEAH-Box Helicase 37defects (DXH37) Defects Are a Novel Cause of 46,XY Gonadal Dysgenesis

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dc.contributor.authorGomes, Nathalia
dc.contributor.authorSilva, Thatiana
dc.contributor.authorLerario, Antonio
dc.contributor.authorBatista, Rafael Loch
dc.contributor.authorFaria Junior, Jose Antonio
dc.contributor.authorMoraes, Daniela
dc.contributor.authorFrade Costa, Elaine Maria
dc.contributor.authorNishi, Mirian
dc.contributor.authorCarvalho, Luciani Renata
dc.contributor.authorVeronica Forclaz, Maria
dc.contributor.authorPapazian, Regina
dc.contributor.authorMartinez Aguayo, Alejandro
dc.contributor.authorde Paula, Leila Pedroso
dc.contributor.authorCarvalho, Filomena Marino
dc.contributor.authorVilain, Erick
dc.contributor.authorBarseghyan, Hayk Barseghyan
dc.contributor.authorKeegan, Catherine
dc.contributor.authorDomenice, Sorahia
dc.contributor.authorMendonca, Berenice Bilharinho
dc.date.accessioned2024-01-10T14:24:24Z
dc.date.available2024-01-10T14:24:24Z
dc.date.issued2018
dc.description.abstractBackground: 46,XY gonadal dysgenesis (GD) is a spectrum disorder which lead to variable degrees of atypical external genitalia, ranging from female to micropenis and absent of gonadal tissue (known as Embryonic Testicular Regression Syndrome -ETRS). Most patients with 46,XY GD remains without a molecular diagnosis.Objective: To report the DEAH-box helicase 37 gene (DHX37) as a novel candidate for the GD etiology.Patients and methods: We studied 12 familial cases from 6 non-consanguineous families by whole exome sequencing, one familial case and 69 sporadic cases by target massively parallel sequencing, including 41 patients with GD, 16 patients with ETRS and 32 patients classified as 46,XY disorder of sex development of unknown etiology (UDSD) due to previous gonadectomy or an inconclusive hormone profile. An amplicon-based capture panel of 63 genes related to DSD for targeted sequencing was used. Sequencing was performed in the Illumina platforms. Paired-end reads were aligned to the hg19 assembly of the human genome with BWA-MEM. Variants were called and annotated with Platypus and ANNOVAR, respectively. Two sporadic cases and one family with ETRS had DHX37 studied by Sanger sequencing. Eighty-seven patients were Brazilian, including 6 families, one sporadic case was Chinese-American and two families were Argentinean and Chilean.Results: Six different missense variants in DHX37 were identified in 8 sporadic cases and in 11 patients from 5 families. All variants are absent or in low frequency (<0.0002) in population (gnomAD) and Brazilian databases and are classified as deleterious by at least 8 prediction tools. The variant p.R308Q was recurrent in 2 non-related ETRS families and in three sporadic cases, including the Chinese-American patient. The p.R674W also recurred in the Argentinean and Chilean ETRS families and in one sporadic GD patient, who also bored a novel GATA4 p.P368R. Another three DHX37 variants were identified in three sporadic UDSD patients and one of them also harbored the novel NR5A1 p.G26V. All these variants are heterozygous and the segregated ones disclosed an autosomal dominant inheritance. One sporadic case of ETRS from a consanguineous family was homozygous for the DHX37 p.R151W. DHX37 is expressed in germ cells at different stages of maturation, as shown by immunohistochemical analysis.Conclusion: The identification of several deleterious variants in DHX37, as monogenic or in digenic inheritance in familial and sporadic cases of 46,XY DSD patients from different parentage, reinforces it is a strong candidate gene for the spectrum of GD phenotypes.
dc.fechaingreso.objetodigital2024-05-03
dc.format.extent2 páginas
dc.fuente.origenWOS
dc.identifier.eissn1663-2826
dc.identifier.issn1663-2818
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/80220
dc.identifier.wosidWOS:000445204100106
dc.information.autorucFacultad de Medicina; Martinez Aguayo, Alejandro Gregorio; S/I; 1003862
dc.language.isoen
dc.nota.accesoSin adjunto
dc.pagina.final53
dc.pagina.inicio52
dc.publisherKARGER
dc.rightsacceso restringido
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleDEAH-Box Helicase 37defects (DXH37) Defects Are a Novel Cause of 46,XY Gonadal Dysgenesis
dc.typecomunicación de congreso
dc.volumen90
sipa.codpersvinculados1003862
sipa.indexWOS
sipa.trazabilidadCarga SIPA;09-01-2024
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