PaternalGNASMutations Lead to Severe Intrauterine Growth Retardation (IUGR) and Provide Evidence for a Role of XLαs in Fetal Development
| Autor: | Arnaud Molin, Nicolas Richard, Harald Jüppner, Marie-Laure Kottler, Nadia Coudray, Pauline Rault-Guillaume |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male musculoskeletal diseases Heterozygote medicine.medical_specialty Adolescent Endocrinology Diabetes and Metabolism Clinical Biochemistry Context (language use) medicine.disease_cause Progressive osseous heteroplasia Biochemistry Fetal Development Endocrinology Internal medicine Chromogranins GTP-Binding Protein alpha Subunits Gs medicine GNAS complex locus Humans Allele Child Alleles Pseudohypoparathyroidism Retrospective Studies Genetics Mutation Fetal Growth Retardation JCEM Online: Advances in Genetics biology Ossification Heterotopic Biochemistry (medical) Infant Newborn Infant Skin Diseases Genetic Exons medicine.disease Bone Diseases Metabolic Child Preschool Infant Small for Gestational Age Pseudopseudohypoparathyroidism biology.protein Severe intrauterine growth retardation Female |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 98:E1549-E1556 |
| ISSN: | 1945-7197 0021-972X |
| Popis: | 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.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.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.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.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. |
| Databáze: | OpenAIRE |
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