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Titolo:
Diverse deletions in the growth hormone receptor gene cause growth hormoneinsensitivity syndrome
Autore:
Gastier, JM; Berg, MA; Vesterhus, P; Reiter, EO; Francke, U;
Indirizzi:
Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 ghes Med Inst, Stanford, CA 94305 USA Vest Agder Hosp, Kristiansand, Norway Vest Agder Hosp Kristiansand Norway st Agder Hosp, Kristiansand, Norway Baystate Med Ctr, Childrens Hosp, Springfield, MA USA Baystate Med Ctr Springfield MA USA Childrens Hosp, Springfield, MA USA Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 d, Dept Genet, Stanford, CA 94305 USA
Titolo Testata:
HUMAN MUTATION
fascicolo: 4, volume: 16, anno: 2000,
pagine: 323 - 333
SICI:
1059-7794(2000)16:4<323:DDITGH>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
GH-BINDING PROTEIN; FACTOR-I; LARON-SYNDROME; FUNCTIONAL-CHARACTERIZATION; SHORT STATURE; IGF-I; MUTATION; DWARFISM; LESSONS; DOMAIN;
Keywords:
growth hormone receptor; GHR; growth hormone insensitivity syndrome; GHIS; Laron syndrome; intragenic deletions; molecular diagnosis; GHR exon 3 deletion polymorphism;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Francke, U Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 st, Stanford, CA 94305 USA
Citazione:
J.M. Gastier et al., "Diverse deletions in the growth hormone receptor gene cause growth hormoneinsensitivity syndrome", HUM MUTAT, 16(4), 2000, pp. 323-333

Abstract

Growth hormone insensitivity syndrome (GHIS; also known as Laron syndrome), is characterized by severe postnatal growth failure and normal growth hormone. The syndrome is frequently caused by point mutations in the growth hormone receptor gene (GHR). Here we report five families with GHIS and partial deletions of the GHR gene. The deletion breakpoints were sequenced and PCR-based diagnostic tests were developed. In a Cambodian family, a novel deletion removed part of exon 5 and 1.2 kb of the preceding intron. The deletion occurred by recombination within four identical nucleotides. In the mutant transcript, skipping of the truncated exon 5 leads to a frameshift and premature termination codon (PTC), A previously reported discontinuous deletion of GHR exons 3, 5, and 6 was identified in three Oriental Jewish families. An unaffected individual was heterozygous for the exon 5 and 6 deletion, but homozygously deleted for exon 3 suggesting that the exon 3 deletion is a polymorphism. The pathogenic deletion of exons 5 and 6 spans about 7.5kb. Sequence analysis of the breakpoints revealed an imperfect junction between introns 4 and 6, with a four basepair insertion. A novel deletion of 13 nucleotides within exon 9 was identified in a Caucasian girl with GHIS who carries the I153T missense mutation on her other allele, The exon 9 deletion leads to a frameshift and PTC, The predicted protein retains the transmembrane domain and a short cytoplasmic tail. Four family members in three generations were carriers of this deletion, but only two of them were belownormal for height, suggesting that this mutation by itself does not act asa dominant negative, as was reported for two other GHR mutations which lead to truncation of the intracellular domain. Hum Mutat 16:323-333, 2000, (C) 2000 Wiley-Liss, Inc.

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Documento generato il 27/11/20 alle ore 13:36:04