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The Journal of Clinical Endocrinology... Sep 2013Heterozygous GNAS inactivating mutations cause pseudohypoparathyroidism type Ia (PHP-Ia) when maternally inherited and pseudopseudohypoparathyroidism (PPHP)/progressive...
CONTEXT
Heterozygous GNAS inactivating mutations cause pseudohypoparathyroidism type Ia (PHP-Ia) when maternally inherited and pseudopseudohypoparathyroidism (PPHP)/progressive osseous heteroplasia (POH) when paternally inherited. Recent studies have suggested that mutations on the paternal, but not the maternal, GNAS allele could be associated with intrauterine growth retardation (IUGR) and thus small size for gestational age.
OBJECTIVES
The aim of the study was to confirm and expand these findings in a large number of patients presenting with either PHP-Ia or PPHP/POH.
PATIENTS AND METHODS
We collected birth parameters (ie, gestational age, weight, length, and head circumference) of patients with either PHP-Ia (n = 29) or PPHP/POH (n = 26) with verified GNAS mutations. The parental allele carrying the mutation was assessed by investigating the parents or, when a de novo mutation was identified, through informative intragenic polymorphisms.
RESULTS
Heterozygous GNAS mutations on either parental allele were associated with IUGR. However, when these mutations are located on the paternal GNAS allele, IUGR was considerably more pronounced than with mutations on the maternal allele. Moreover, birth weights were lower with paternal GNAS mutations affecting exons 2-13 than with exon 1/intron 1 mutations.
CONCLUSIONS
These data indicate that a paternally derived GNAS transcript, possibly XLαs, is required for normal fetal growth and development and that this transcript affects placental functions. Thus, similar to other imprinted genes, GNAS controls growth and/or fetal development.
Topics: Adolescent; Adult; Alleles; Bone Diseases, Metabolic; Child; Child, Preschool; Chromogranins; Exons; Female; Fetal Development; Fetal Growth Retardation; GTP-Binding Protein alpha Subunits, Gs; Heterozygote; Humans; Infant; Infant, Newborn; Infant, Small for Gestational Age; Male; Mutation; Ossification, Heterotopic; Pseudopseudohypoparathyroidism; Retrospective Studies; Skin Diseases, Genetic
PubMed: 23884777
DOI: 10.1210/jc.2013-1667 -
Journal of Bone and Mineral Research :... Jun 1997
Topics: Female; Humans; Infant; Metacarpus; Osteoma; Phenotype; Pseudopseudohypoparathyroidism; Radiography; Skin Neoplasms
PubMed: 9169361
DOI: 10.1359/jbmr.1997.12.6.995 -
Indian Journal of Dermatology,... 2020
Topics: Adult; Bone Diseases, Metabolic; Humans; Male; Ossification, Heterotopic; Scalp; Skin Diseases, Genetic
PubMed: 31608898
DOI: 10.4103/ijdvl.IJDVL_682_18 -
Journal of the Royal Society of Medicine Feb 1994
Topics: Acne Vulgaris; Facial Neoplasms; Female; Humans; Middle Aged; Osteoma
PubMed: 8196025
DOI: No ID Found -
Indian Journal of Dermatology,... 2017
Topics: Asymptomatic Diseases; Bone Diseases, Metabolic; Cheek; Female; Humans; Middle Aged; Ossification, Heterotopic; Skin Abnormalities; Skin Diseases, Genetic
PubMed: 28440231
DOI: 10.4103/ijdvl.IJDVL_432_16