Loss-of-function mutations in the human GLI2 gene are associated with pituitary anomalies and holoprosencephaly-like features

Erich Roessler, Yang Zhu Du, Jose L. Mullor, Esther Casas, William P. Allen, Gabriele Gillessen-Kaesbach, Elizabeth R. Roeder, Jeffrey E. Ming, Ariel Ruiz I Altaba, Maximilian Muenke*

*Korrespondierende/r Autor/-in für diese Arbeit
251 Zitate (Scopus)

Abstract

Diminished Sonic Hedgehog (Shh) signaling is associated with the most common forebrain defect in humans, holoprosencephaly (HPE), which includes cyclopia, a phenotype also seen in mice and other vertebrates with defective Shh signaling. The secreted protein Shh acts as a crucial factor that patterns the ventral forebrain and is required for the division of the primordial eye field and brain into two discrete halves. Gli2 is one of three vertebrate transcription factors implicated as obligatory mediators of Shh signal transduction. Here, we show that loss-of-function mutations in the human GLI2 gene are associated with a distinctive phenotype (within the HPE spectrum) whose primary features include defective anterior pituitary formation and pan-hypopituitarism, with or without overt forebrain cleavage abnormalities, and HPE-like midfacial hypoplasia. We also demonstrate that these mutations lack GLI2 activity. We report on a functional association between GLI2 and human disease and highlight the role of GLI2 in human head development.

OriginalspracheEnglisch
ZeitschriftProceedings of the National Academy of Sciences of the United States of America
Jahrgang100
Ausgabenummer23
Seiten (von - bis)13424-13429
Seitenumfang6
ISSN0027-8424
DOIs
PublikationsstatusVeröffentlicht - 11.11.2003

Strategische Forschungsbereiche und Zentren

  • Querschnittsbereich: Medizinische Genetik

Fingerprint

Untersuchen Sie die Forschungsthemen von „Loss-of-function mutations in the human GLI2 gene are associated with pituitary anomalies and holoprosencephaly-like features“. Zusammen bilden sie einen einzigartigen Fingerprint.

Zitieren