A novel mutation in IGFALS, c.380TC (p.L127P), associated with short stature, delayed puberty, osteopenia and hyperinsulinaemia in two siblings: insights into the roles of insulin growth factor-1 (IGF1)
| Autor: | Morad Khayat, Karen E. Heath, Ora Hess, Vivian Hwa, Yardena Tenenbaum-Rakover, Yifat Hritan, Stavit Allon-Shalev, Amnon Teitler |
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| Rok vydání: | 2013 |
| Předmět: |
Delayed puberty
Proband Male medicine.medical_specialty Adolescent Endocrinology Diabetes and Metabolism medicine.medical_treatment IGFBP3 Mutation Missense Biology Short stature Cohort Studies Consanguinity Endocrinology Diabetes mellitus Internal medicine Hyperinsulinism medicine Humans Insulin-Like Growth Factor I Child Dwarfism Pituitary Glycoproteins Puberty Delayed Insulin Siblings Homozygote Infant Syndrome medicine.disease Idiopathic short stature Osteopenia Bone Diseases Metabolic Amino Acid Substitution Child Preschool Female medicine.symptom Carrier Proteins |
| Zdroj: | Clinical endocrinology. 79(6) |
| ISSN: | 1365-2265 |
| Popis: | SummaryBackground The acid-labile subunit (ALS) protein is crucial for maintaining the circulating IGF/IGFBP system. Inactivating mutations of IGFALS result in IGF1 deficiency associated with growth retardation. Although the first IGFALS mutation in humans was described in 2004, only 16 mutations have been reported since. Moreover, the phenotype of affected patients as a consequence of ALS deficiency is still highly variable. We assessed whether children with idiopathic short stature (ISS) harbour mutations in IGFALS and characterized affected patients' phenotype. Design Sixty-five children with ISS were enrolled in the study. Serum ALS levels were measured by ELISA, and IGFALS was sequenced. Results A novel homozygous mutation in IGFALS, c.380T>C (p.L127P), was identified in two siblings of a consanguineous family. The proband, a 17·75-year-old male, was −1·9 SDS in height and −4·5 SDS in weight. Exaggerated stimulated GH (38 ng/ml) and extremely low IGF1 and IGFBP3 ( |
| Databáze: | OpenAIRE |
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