
Fulltext:
69990.pdf
Embargo:
until further notice
Size:
317.9Kb
Format:
PDF
Description:
publisher's version
Publication year
2008Source
European Journal of Endocrinology, 159, 2, (2008), pp. 113-120ISSN
Publication type
Article / Letter to editor

Display more detailsDisplay less details
Organization
Human Genetics
Endocrinology
Paediatrics - OUD tm 2017
Medical Psychology
Journal title
European Journal of Endocrinology
Volume
vol. 159
Issue
iss. 2
Page start
p. 113
Page end
p. 120
Subject
IGMD 5: Health aging / healthy living; IGMD 6: Hormonal regulation; IGMD 8: Mitochondrial medicine; UMCN 5.1: Genetic defects of metabolism; UMCN 5.2: Endocrinology and reproductionAbstract
CONTEXT: Acid-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. OBJECTIVE: To 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. SUBJECTS: Three short Kurdish brothers and their relatives. RESULTS: The 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. CONCLUSIONS: The 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.
This item appears in the following Collection(s)
- Academic publications [203856]
- Electronic publications [102313]
- Faculty of Medical Sciences [80326]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.