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
Baz-Redón, Noelia (Hospital Universitari Vall d'Hebron)
Soler-Colomer, Laura (Hospital Universitari Vall d'Hebron)
Fernández Cancio, Mónica (Hospital Universitari Vall d'Hebron)
Benito-Sanz, Sara (Hospital Universitario La Paz (Madrid))
Garrido-Marin, Marta (Hospital Universitari Vall d'Hebron)
Moliné, Teresa (Hospital Universitari Vall d'Hebron)
Clemente, Maria (Hospital Universitari Vall d'Hebron)
Camats Tarruella, Núria (Hospital Universitari Vall d'Hebron)
Yeste Fernández, Diego (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Fecha:	2022
Resumen:	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.
Ayudas:	Ministerio de Economía y Competitividad PI15/01647
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	46,XY different sexual development ; Case report ; HHAT ; Minigene studies ; Syndromic DSD
Publicado en:	Frontiers in endocrinology, Vol. 13 (october 2022) , ISSN 1664-2392

DOI: 10.3389/fendo.2022.957969
PMID: 36303863

8 p, 4.1 MB

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