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Shortened Fingers and Toes: GNAS Abnormalities are Not the Only Cause
- Source :
- Exp Clin Endocrinol Diabetes
- Publication Year :
- 2019
- Publisher :
- Georg Thieme Verlag KG, 2019.
-
Abstract
- The PTH/PTHrP receptor (PTHR1) mediates the actions of parathyroid hormone (PTH) and PTH-related peptide (PTHrP) by coupling this G protein-coupled receptor (GPCR) to the alpha-subunit of the heterotrimeric stimulatory G protein (Gsα) and thereby to the formation of cAMP. In growth plates, PTHrP-dependent activation of the cAMP/PKA second messenger pathway prevents the premature differentiation of chondrocytes into hypertrophic cells resulting in delayed growth plate closure. Heterozygous mutations in GNAS, the gene encoding Gsα, lead to a reduction in cAMP levels in growth plate chondrocytes that is sufficient to cause shortening of metacarpals and/or -tarsals, i. e. typical skeletal aspects of Albright’s Hereditary Osteodystrophy (AHO). However, heterozygous mutations in other genes, including those encoding PTHrP, PRKAR1A, PDE4D, and PDE3A, can lead to similar or even more pronounced acceleration of skeletal maturation that is particularly obvious in hands and feet, and reduces final adult height. Genetic mutations other than those resulting in Gsα haploinsufficiency thus reduce intracellular cAMP levels in growth plate chondrocytes to a similar extent and thereby accelerate skeletal maturation.
- Subjects :
- musculoskeletal diseases
0301 basic medicine
medicine.medical_specialty
Gs alpha subunit
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
Endocrinology, Diabetes and Metabolism
Acrodysostosis
Parathyroid hormone
030105 genetics & heredity
Article
Fingers
03 medical and health sciences
Chondrocytes
Endocrinology
Internal medicine
Heterotrimeric G protein
Chromogranins
GTP-Binding Protein alpha Subunits, Gs
Internal Medicine
medicine
GNAS complex locus
Humans
Growth Plate
Receptor
PRKAR1A
Receptor, Parathyroid Hormone, Type 1
biology
Chemistry
Parathyroid Hormone-Related Protein
General Medicine
Toes
medicine.disease
Cyclic AMP-Dependent Protein Kinases
Cyclic Nucleotide Phosphodiesterases, Type 3
Cyclic Nucleotide Phosphodiesterases, Type 4
Musculoskeletal Abnormalities
030104 developmental biology
biology.protein
Haploinsufficiency
hormones, hormone substitutes, and hormone antagonists
Subjects
Details
- ISSN :
- 14393646 and 09477349
- Volume :
- 128
- Database :
- OpenAIRE
- Journal :
- Experimental and Clinical Endocrinology & Diabetes
- Accession number :
- edsair.doi.dedup.....a390e854a8607b8afab4b13887bbe39f