A Genotype-First Approach for Clinical and Genetic Evaluation of Wolcott-Rallison Syndrome in a Large Cohort of Iranian Children With Neonatal Diabetes
| Autor: | Sima Parvizi Omran, Maryam Razzaghy-Azar, Aria Sotodeh, Farzaneh Abbasi, Samaneh Enayati, Maryam Habibi, Mahsa M. Amoli, Reza Maroofian, Fatemeh Bitarafan |
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| Rok vydání: | 2018 |
| Předmět: |
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Proband Pediatrics medicine.medical_specialty Endocrinology Diabetes and Metabolism DNA Mutational Analysis 030209 endocrinology & metabolism Iran Osteochondrodysplasias Short stature Cohort Studies eIF-2 Kinase 03 medical and health sciences 0302 clinical medicine Endocrinology Diabetes Mellitus Internal Medicine medicine Humans Family history Genetic testing medicine.diagnostic_test business.industry Genotype-first approach Infant General Medicine Permanent neonatal diabetes mellitus medicine.disease Diabetes Mellitus Type 1 Failure to thrive Female medicine.symptom business Epiphyses Wolcott–Rallison syndrome 030217 neurology & neurosurgery |
| Zdroj: | Canadian Journal of Diabetes. 42:272-275 |
| ISSN: | 1499-2671 |
| DOI: | 10.1016/j.jcjd.2017.06.009 |
| Popis: | OBJECTIVE Wolcott-Rallison syndrome (WRS) is an extremely rare autosomal recessive condition, characterized by permanent neonatal diabetes mellitus (PNDM) associated with skeletal dysplasia, growth retardation and liver dysfunction. WRS is caused by biallelic mutations in the gene encoding eukaryotic translation initiation factor 2alpha kinase 3 (EIF2AK3). METHODS As part of a comprehensive study on clinical and genetic investigation of neonatal diabetes in an Iranian population, 60 unrelated Iranian subjects referred with PNDM were analyzed. All the probands were screened for KCNJ11, INS, ABCC8 and EIF2AK3 using a polymerase chain reaction-based sequencing approach. RESULTS We identified 9 different variants in EIF2AK3 in 11 unrelated Iranian probands, of which 5 variants were shown to be novel and not reported previously. The diagnosis of WRS was made by molecular genetic testing and confirmed by clinical re-evaluation of the subjects. Clinical follow up of the affected individuals shows that in at least some of them, PNDM was associated with short stature, failure to thrive, neurodevelopmental delay, epilepsy and hepatic and renal dysfunction. There was a strong family history of neonatal diabetes in the families of the probands with a high mortality rate. CONCLUSION WRS is a common cause of PNDM in children of consanguineous parents. Furthermore, clinical diagnosis of WRS would have been delayed or possibly missed without genetic testing because this study shows that the associated features of WRS might be obscured by a diagnosis of PNDM. Therefore EIF2AK3 should be considered for any infant and young child with PNDM, particularly if the parents are related. |
| Databáze: | OpenAIRE |
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