Novel variant in HHAT as a cause of different sex development with partial gonadal dysgenesis associated with microcephaly, eye defects, and distal phalangeal hypoplasia of both thumbs: Case report
| Autor: | Baz Redón, Noelia, Soler Colomer, Laura, Fernández Cancio, Mónica, Benito-Sanz, Sara, Garrido-Pontnou, Marta, Moline Marimon, Teresa, Clemente Leon, Maria, Camats Tarruella, Nuria, Yeste Fernandez, Diego |
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| Přispěvatelé: | Institut Català de la Salut, [Baz-Redón N] Grup de Recerca en Creixement i Desenvolupament, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Pediatria, Ginecologia i Obstetrícia i Medicina Preventiva, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Soler-Colomer L] Unitat d’Endocrinologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Fernández-Cancio M, Camats-Tarruella N] Grup de Recerca en Creixement i Desenvolupament, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Benito-Sanz S] Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autonóma de Madrid, Madrid, Spain. [Garrido M, Moliné T] Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Clemente M, Yeste D] Grup de Recerca en Creixement i Desenvolupament, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Pediatria, Ginecologia i Obstetrícia i Medicina Preventiva, Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat d’Endocrinologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Rok vydání: | 2022 |
| Předmět: |
Trastorns del desenvolupament
Crani - Malformacions Turner Síndrome de Endocrinology Diabetes and Metabolism fenómenos fisiológicos::crecimiento y desarrollo::desarrollo sexual [FENÓMENOS Y PROCESOS] Endocrine System Diseases::Gonadal Disorders::Disorders of Sex Development::Gonadal Dysgenesis [DISEASES] enfermedades del sistema endocrino::trastornos gonadales::trastornos del desarrollo sexual::disgenesia gonadal [ENFERMEDADES] Musculoskeletal Diseases::Musculoskeletal Abnormalities::Craniofacial Abnormalities::Microcephaly [DISEASES] enfermedades musculoesqueléticas::anormalidades musculoesqueléticas::anomalías craneofaciales::microcefalia [ENFERMEDADES] Physiological Phenomena::Growth and Development::Sexual Development [PHENOMENA AND PROCESSES] |
| Zdroj: | Scientia |
| ISSN: | 1664-2392 |
| DOI: | 10.3389/fendo.2022.957969 |
| Popis: | Different sexual development; Minigene studies Desarrollo sexual diferente; Estudios de minigenes Desenvolupament sexual diferent; Estudis minigènics The palmitoylation of the Hedgehog (Hh) family of morphogens, named sonic hedgehog (SHH), desert hedgehog (DHH), and Indian hedgehog (IHH), is crucial for effective short- and long-range signaling. The hedgehog acyltransferase (HHAT) attaches the palmitate molecule to the Hh; therefore, variants in HHAT cause a broad spectrum of phenotypes. A missense HHAT novel variant c.1001T>A/p.(Met334Lys) was described in a patient first referred for a 46,XY different sexual development with partial gonadal dysgenesis but with microcephaly, eye defects, and distal phalangeal hypoplasia of both thumbs. The in silico analysis of the variant predicted an affectation of the nearest splicing site. Thus, in vitro minigene studies were carried out, which demonstrated that the variant does not affect the splicing. Subsequent protein in silico studies supported the pathogenicity of the variant, and, in conclusion, this was considered the cause of the patient’s phenotype. This study was partly supported by a grant from the Fondo de Investigación Sanitaria (PI15/01647 [to MF-C and SB-S]). |
| Databáze: | OpenAIRE |
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