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Gene: GNAS complex locus (GNAS1, Gs alpha, NESP55, XLalpha s, GNAS1-AS(SANG), miR-296, miR-298) |
Description: The GNAS1 gene contains three imprinted protein-coding transcripts, one non-coding transcript and
one imprinted antisense transcript.
1. Gs-alpha (a small GTPases) is maternally expressed the pituitary gland (Hayward
BE et al, 2001), thyroid and gonads (Mantovani
G et al. 2002; Liu
J et al, 2003; Germain-Lee
EL et al, 2002), but is biallelically expressed in most other tissues (Hayward
BE et al, Aug 1998). It is likely to be imprinted in the renal proximal tubules (Liu
J et al, 2000). In clones derived from bone marrow stroma, non-imprinted allelic imbalance was
noted in the Gs alpha transcript (Michienzi
S et al, 2007).
2. XLalpha s (the extra-large variant of the G protein alpha-subunit) is paternally expressed (Hayward
BE et al, Aug 1998). Multiple transcripts and protein isoforms are derived from the XL (XXL)
promoter (Abramowitz
J et al, 2004).
3. NESP55 (Neuroendocrine secretory protein 55, a chromogranin-like protein) is maternally expressed
in multiple fetal tissues (Hayward
BE et al, Dec 1998).
4. The exon 1A (exon A/B) transcript is probably not translated and is paternally expressed (Liu
J et al, 2000).
5. GNAS1-AS(SANG) is a paternally expressed antisense transcript that spans the upstream NESP55
region (Hayward
BE et al, 2000).
This transcript hosts two microRNAs. Robson, JE et al, (2012) provided evidence for
exclusive paternal expression of miR-296-5p and miR-298 in two lymphoblastoid human cell lines.
The inheritance pattern of several diseases suggested imprinting of the GNAS1 gene . Albright
hereditary osteodystrophy displays various physical abnormalities as well as end organ resistance to
various hormones including parathyroid (pseudo-hypoparathyroidism type 1a) when inherited maternally
(60 offspring from 33/36 maternal transmitting parents). However when this disease is transmitted
paternally, offspring (6) suffer from the physical features of AHO but lack hormone resistance
(pseudopseudo-hypoparathyroidism) (Davies
SJ et al, 1993). Recent evidence that the Gs-alpha transcript is predominantly maternally
expressed in the thyroid gland and gonads is consistent with this inheritance pattern (Mantovani
G et al. 2002). Progressive osseous heteroplasia is attributable to paternally inherited
mutations of GNAS1 (Shore
EM et al, 2002). Abnormal imprinting (loss of methylation) of a region upstream of the Gs alpha
promoter in exon 1A (exon A/B) has been identified in 13 of 13 patients with
pseudohypoparathyroidism type IB (renal resistance to parathyroid hormone lacking other AHO
associated symptoms) (Liu
J et al, 2000; Bastepe
M et al, 2001). Pseudohypoparathyroidism type IB shows an imprinted inheritance pattern, ie, the
disease is always maternally transmitted (Juppner
H et al, 1998).
For review summaries see Lalande
M, 2001 and Weinstein
LS et al, 2002. |