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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorYeste Fernandez, Diego
dc.contributor.authorAguilar Riera, Cristina
dc.contributor.authorCanestrino, Gennaro
dc.contributor.authorFernández Álvarez, Paula
dc.contributor.authorClemente Leon, Maria
dc.contributor.authorCamats Tarruella, Nuria
dc.date.accessioned2022-09-19T08:08:17Z
dc.date.available2022-09-19T08:08:17Z
dc.date.issued2022-06-28
dc.identifier.citationYeste D, Aguilar-Riera C, Canestrino G, Fernández-Alvarez P, Clemente M, Camats-Tarruella N. A New MAMLD1 Variant in an Infant With Microphallus and Hypospadias With Hormonal Pattern Suggesting Partial Hypogonadotropic Hypogonadism—Case Report. Front Endocrinol. 2022 Jun 28;13:884107.
dc.identifier.issn1664-2392
dc.identifier.urihttp://hdl.handle.net/11351/8212
dc.descriptionMAMLD1 gene; Hypospadias; Minipuberty
dc.description.abstractMAMLD1 (X chromosome) is one of the recognized genes related to different sex development. It is expressed in testis and ovaries and seems to be involved in fetal sex development and in adult reproductive function, including testosterone biosynthesis. However, its exact role remains unclear. Over 40 genetic variants have been described, mainly in male individuals and mostly associated with hypospadias. Although MAMLD1 has been shown to regulate the expression of the steroidogenic pathway, patients with MAMLD1 variants mostly show normal gonadal function and normal testosterone levels. Here we describe a patient (46,XY) with hypospadias and microphallus, with low testosterone and dihydrotestosterone (DHT) levels, and with inappropriately low values of luteinizing hormone (LH) during minipuberty. This hormonal pattern was suggestive of partial hypogonadotropic hypogonadism. A stimulation test with hCG (4 months) showed no significant increase in both testosterone and dihydrotestosterone concentrations. At 5 months of age, he was treated with intramuscular testosterone, and the penis length increased to 3.5 cm. The treatment was stopped at 6 months of age. Our gonadal function massive-sequencing panel detected a previously unreported nonsense variant in the MAMLD1 gene (c.1738C>T:p.Gln580Ter), which was classified as pathogenic. This MAMLD1 variant, predicting a truncated protein, could explain his genital phenotype. His hormonal profile (low testosterone, dihydrotestosterone, and LH concentrations) together with no significant increase of testosterone and DHT plasma concentrations (hCG test) highlight the potential role of this gene in the biosynthesis of testosterone during the fetal stage and minipuberty of the infant. Besides this, the LH values may suggest an involvement of MAMLD1 in the LH axis or a possible oligogenesis. It is the first time that a decrease in DHT has been described in a patient with an abnormal MAMLD1.
dc.language.isoeng
dc.publisherFrontiers Media
dc.relation.ispartofseriesFrontiers in Endocrinology;13
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectHipogonadisme
dc.subjectCromosomes sexuals - Anomalies
dc.subjectAparell genital masculí
dc.subject.meshHypogonadism
dc.subject.meshSexual Development
dc.subject.meshPenis
dc.subject.mesh/abnormalities
dc.titleA New MAMLD1 Variant in an Infant With Microphallus and Hypospadias With Hormonal Pattern Suggesting Partial Hypogonadotropic Hypogonadism—Case Report
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.3389/fendo.2022.884107
dc.subject.decshipogonadismo
dc.subject.decsdesarrollo sexual
dc.subject.decspene
dc.subject.decs/anomalías
dc.relation.publishversionhttps://doi.org/10.3389/fendo.2022.884107
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Yeste D, Clemente M] Unitat d’Endocrinologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. CIBER of Rare Diseases (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Aguilar-Riera C] Unitat d’Endocrinologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Canestrino G] Paediatric Endocrinology Service, Paediatric Service, Sant Joan de Déu Manresa Hospital, Manresa, Spain. [Fernández-Alvarez P] Laboratori de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Camats-Tarruella N] CIBER of Rare Diseases (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Grup de Recerca en Creixement i Desenvolupament, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain
dc.identifier.pmid35837313
dc.identifier.wos000824171000001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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