Avtor/Urednik     Kržišnik, Ciril; Kolacio, Zdravka; Battelino, Tadej; Brown, Milton; Parks, John S; Laron, Zvi
Naslov     The "little people" of the Island of Krk - revisited. Etiology of hypopituitarism revealed
Tip     članek
Vir     Journal Endoc Gen
Vol. in št.     Letnik 1, št. 1
Leto izdaje     1999
Obseg     str. 9-19
Jezik     eng
Abstrakt     Hereditary dwarfism was first recognized in inhabitants of the island of Krk in the Adriatic in 1864. Since then 24 related dwarfs have been recorded. Their pedigrees and heights are presented. Ten of these patients live in the villages Baščanska Draga and Jurandvor. Six have been studied by the authors. Clinical examination revealed dwarfism, obesity, dry wrinkled skin, and lack of sexual development. Hormonal investigations showed the absence of growth hormone (GH) unresponsive to growth hormone releasing hormone (GNRH), absence of luteinizing hormone (LH) and follicle stimulating hormone (FSH) unresponsive to gonadotropin releasing hormone (GnRH), and absence of thyrotropin stimulating hormone (TSH) unresponsive ro TRH. Basal serum prolactin (PRL) was low but secretion of ACTH was normal as evidenced by normal cortisol levels. Hypopituitarism in this isolate was not associeted with a shortened life span or an increased incidence of diabetes. PROP-1 is a pituitary specific transcription factor that is required for the embryologic development of the pituitary cell types that ultimately produce GH, PRL, TSH and FSH/LH postanatally. ExaminatuÐion of genomic DNA from two of the patients revealed homozygosity for a one bp deletion in codon 50 of exon 2 of PROP-1. This introduces a frame shift and results in a premature translational stop signal at codon 164. The truncated protein lacks the DNA-binding and transcriptional activation domains. In conclusion, basic insights into the transcription factors contributing to pituitary development led to definition of hereditary multiple pituitary hormoone deficiency (MPHD) dwarfism on the island of Krk. The hypopituitarism is due to a mutation in the PROP-1 gene. This genetic isolate provides a unique opportunity to characterize the long-term effects of hypopituitarism caused by PROP-1 deficiency.
Deskriptorji     DWARFISM, PITUITARY
AXONS
HYPOPITUITARISM
PEDIGREE
BODY HEIGHT
POLYMERASE CHAIN REACTION
THYROID FUNCTION TESTS
DNA
ANTISENSE ELEMENTS (GENETICS)
CROATIA