Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
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
Ist Teil von
Frontiers in endocrinology (Lausanne), 2022-10, Vol.13
Ort / Verlag
Frontiers Media S.A
Erscheinungsjahr
2022
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
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.