Atypical STAT5B deficiency, severe short stature and mild immunodeficiency associated with a novel homozygous STAT5B Variant
Yükleniyor...
Tarih
2022
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier Ireland Ltd
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
STAT5B deficiency, a rare autosomal recessive disorder characterized by severe growth hormone insensitivity (GHI) and immunodeficiency, can manifest as fatal pulmonary complications. We describe atypical STAT5B deficiency associated with a novel homozygous frame-shift STAT5B variant [c.1453delG, p.(Asp485Thrfs*29)] identified in a young 17.6 yr old female subject who had severe postnatal growth impairment, biochemistries typical of GHI, an immune profile notable for hypergammaglobulinaemia and elevated B lymphocytes, and lack of pulmonary disease. Marked elevation of serum prolactin and pathologically diagnosed eczema were evident. In reconstitution studies, the STAT5B p.(Asp485Thrfs*29) was expressed although expression was reduced compared to wild-type STAT5B and a previously identified STAT5B p.(Gln368Profs*9) variant. Both truncated STAT5B peptides could not be activated by GH, nor mobilize to the nucleus. We conclude that an intact, functional, STAT5B is essential for normal GH-mediated growth, while expressed loss-of-function STAT5B variants may alleviate severe immune and pulmonary issues normally associated with STAT5B deficiency.
Açıklama
Anahtar Kelimeler
Growth Hormone Insensitivity, Immune Deficiency, STAT5B
Kaynak
Molecular and Cellular Endocrinology
WoS Q Değeri
Q2
Scopus Q Değeri
N/A
Cilt
559
Sayı
Künye
Catli, G., Gao, W., Foley, C., Özyilmaz, B., Edeer, N., Diniz, G., . . . Hwa, V. (2023). Atypical STAT5B deficiency, severe short stature and mild immunodeficiency associated with a novel homozygous STAT5B variant. Molecular and Cellular Endocrinology, 559 doi:10.1016/j.mce.2022.111799
