Homozygous and heterozygous expression of a novel mutation of the acid-labile subunit
| Autor: | Th.B. Twickler, H.A. van Duyvenvoorde, J. van Doorn, Marlies Kempers, Marcel Karperien, W J Gerver, Ad R. M. M. Hermus, Cees Noordam, Monique Losekoot, J.M. Wit |
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| Přispěvatelé: | Amsterdam Cardiovascular Sciences, Vascular Medicine, Kindergeneeskunde, RS: NUTRIM - R1 - Metabolic Syndrome |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male medicine.medical_specialty Microcephaly Heterozygote Health aging / healthy living [IGMD 5] Adolescent Endocrinology Diabetes and Metabolism Context (language use) Dwarfism Biology medicine.disease_cause Short stature METIS-253639 Loss of heterozygosity Consanguinity Endocrinology Insulin resistance Internal medicine Gene expression medicine Humans Family Child Gene Glycoproteins Mutation Endocrinology and reproduction [UMCN 5.2] Homozygote Hormonal regulation [IGMD 6] General Medicine Middle Aged medicine.disease Pedigree Phenotype Mitochondrial medicine [IGMD 8] Genetic defects of metabolism [UMCN 5.1] Child Preschool Female Human medicine medicine.symptom Carrier Proteins |
| Zdroj: | European Journal of Endocrinology, 159, 113-20 European Journal of Endocrinology, 159, 2, pp. 113-20 European journal of endocrinology European journal of endocrinology / European Federation of Endocrine Societies, 159(2), 113-120. BioScientifica Ltd. European journal of endocrinology, 159(2), 113-120. BioScientifica Ltd. European Journal of Endocrinology, 159(2), 113-20. BioScientifica Ltd. |
| ISSN: | 0804-4643 |
| Popis: | ContextAcid-labile subunit (ALS) deficiency due to homozygous inactivation of the ALS gene (IGFALS) is associated with moderate short stature, and in few cases pubertal delay. The clinical expression of heterozygosity is unknown.ObjectiveTo investigate the clinical, laboratory, and radiological features of homozygous and heterozygous carriers of a novel mutation in the ALS gene in comparison with non-carriers.SubjectsThree short Kurdish brothers and their relatives.ResultsThe index cases presented with short stature, microcephaly, and low circulating IGF-I and IGF-binding protein-3 (IGFBP-3), and undetectable ALS levels. Two were known with a low bone mineral density and one of them had suffered from two fractures. We found a novel homozygous ALS gene mutation resulting in a premature stop codon (c.1490dupT, p.Leu497PhefsX40). The IGF-I, IGFBP-3, and ALS 150 kDa ternary complex was absent, and ALS proteins in serum were not detected with western blot. IGFPB-1 and IGFPB-2 were low and there was a mild insulin resistance. Five heterozygous carriers tended to have a lower height and head circumference than five non-carriers, and had low plasma ALS and IGFBP-3 levels. Bone mineral (apparent) density was low in two out of three homozygous carriers, and also in four out of nine relatives.ConclusionsThe clinical presentation of homozygous ALS mutations may, besides short stature, include microcephaly. Heterozygous carriers may have less statural and head growth, suggestive for a gene dosage effect. |
| Databáze: | OpenAIRE |
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