We have located links that may give you full text access.
A Genotype-First Approach for Clinical and Genetic Evaluation of Wolcott-Rallison Syndrome in a Large Cohort of Iranian Children With Neonatal Diabetes.
Canadian Journal of Diabetes 2018 June
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.
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.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app