FOXP3 mutations causing early-onset insulin-requiring diabetes but without other features of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome.
Pediatr Diabetes
; 19(3): 388-392, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29193502
ABSTRACT
Diabetes occurs in 1/90 000 to 1/160 000 births and when diagnosed under 6 months of age is very likely to have a primary genetic cause. FOXP3 encodes a transcription factor critical for T regulatory cell function and mutations are known to cause "immune dysregulation, polyendocrinopathy (including insulin-requiring diabetes), enteropathy, X-linked" (IPEX) syndrome. This condition is often fatal unless patients receive a bone-marrow transplant. Here we describe the phenotype of male neonates and infants who had insulin-requiring diabetes without other features of IPEX syndrome and were found to have mutations in FOXP3. Whole-exome or next generation sequencing of genes of interest was carried out in subjects with isolated neonatal diabetes without a known genetic cause. RT-PCR was carried out to investigate the effects on RNA splicing of a novel intronic splice-site variant. Four male subjects were found to have FOXP3 variants in the hemizygous state p.Arg114Trp, p.Arg347His, p.Lys393Met, and c.1044+5G>A which was detected in 2 unrelated probands and in a brother diagnosed with diabetes at 2.1 years of age. Of these, p.Arg114Trp is likely a benign rare variant found in individuals of Ashkenazi Jewish ancestry and p.Arg347His has been previously described in patients with classic IPEX syndrome. The p.Lys393Met and c.1044+5G>A variants are novel to this study. RT-PCR studies of the c.1044+5G>A splice variant confirmed it affected RNA splicing by generating both a wild type and truncated transcript. We conclude that FOXP3 mutations can cause early-onset insulin-requiring diabetes with or without other features of IPEX syndrome.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sistema de Registros
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Doenças Genéticas Ligadas ao Cromossomo X
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Diabetes Mellitus
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Diabetes Mellitus Tipo 1
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Diarreia
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Fatores de Transcrição Forkhead
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Doenças do Sistema Imunitário
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
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Infant
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Male
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Newborn
Idioma:
En
Revista:
Pediatr Diabetes
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article