| Diabetes caused by Insulin gene (INS) deletion: clinical characteristics of homozygous and heterozygous individuals. | |
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MedLine Citation:
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PMID: 21566073 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Background: Mutations of the preproinsulin gene (INS) account for both permanent neonatal diabetes (PND) and adult-onset diabetes. The molecular mechanism of complete INS-deletion has recently been published and we now add clinical data of homozygous and heterozygous subjects as well as the detailed mapping of the 646 bp deletion of the INS gene. Methods: Location and size of the INS-deletion was mapped in one case with PND and INS-genotype of the whole family was further characterized by breakpoint-spanning PCR. The phenotype of monoallelic loss of INS was studied in 33 adult family members of the large consanguineous kindred with INS deletion. Results: The 646 bp deletion was found in two individuals with PND which included exon 1 and exon 2 of the INS gene (chr11: g.2138434_2139080del646) and results in loss of approximately half of the preproinsulin protein. The two boys with homozygous INS-deletion (D/D) presented with reduced birth weight, PND within the first 24 hrs of life and complete absence of c-peptide. Adult family members with the INS/D had diabetes onset with earliest 25 yrs, while the oldest subject without diabetes was 45 yrs. INS-deletion-diabetes was initially treated with OADs but then transferred to insulin within 5 to 16 yrs. Overall, INS/D-subjects (N=11) had a higher risk to develop insulin-dependent diabetes up to the fifth decade, if compared to normal subjects (N=22). Conclusion: Complete loss of the human INS gene results in neonatal diabetes, while heterozygous INS-deletion is a strong risk factor for developing insulin-dependent diabetes at adult age. |
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Authors:
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Klemens Raile; Michele O Connell; Angela Galler; George Werther; Peter Kühnen; Heiko Krude; Oliver Blankenstein |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-12 |
Journal Detail:
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Title: European journal of endocrinology / European Federation of Endocrine Societies Volume: - ISSN: 1479-683X ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-5-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9423848 Medline TA: Eur J Endocrinol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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K Raile, Paediatric Endocrinology, Charite, Berlin, 13353, Germany. |
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