Extended clinical features associated with novel Glis3 mutation: a case report

A B Alsaedi,A Altawil,A Aljasser,Naglaa M Kamal,K A Alghamdi

doi:10.1186/s12902-017-0160-z

A B Alsaedi, A Altawil + Show 3 more

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https://doi.org/10.1186/s12902-017-0160-z

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Abstract

BackgroundMutations in the GLI-similar 3 (GLIS3) gene encoding the transcription factor GLIS3 are a rare cause of neonatal diabetes and congenital hypothyroidism with 12 reported patients to date. Additional features, previously described, include congenital glaucoma, hepatic fibrosis, polycystic kidneys, developmental delay, facial dysmorphism, osteopenia, sensorineural deafness, choanal atresia, craniosynostosis and pancreatic exocrine insufficiency.Case presentationWe report a new case for consanguineous parents with homozygous novel mutation in GLIS3 gene who presented with neonatal diabetes mellitus, severe resistant congenital hypothyroidism, cholestatic liver disease, bilateral congenital glaucoma and facial dysmorphism. There were associated abnormalities in the external genitalia in form of bifid scrotum, bilateral undescended testicles, microphallus and scrotal hypospadias which might be a coincidental finding.ConclusionsWe suggest that infants with neonatal diabetes associated with dysmorphism should be screened for GLIS3 gene mutations.

Highlights

Mutations in the GLI-similar 3 (GLIS3) gene encoding the transcription factor GLIS3 are a rare cause of neonatal diabetes and congenital hypothyroidism with 12 reported patients to date
We suggest that infants with neonatal diabetes associated with dysmorphism should be screened for GLIS3 gene mutations
The 10 coding exons of the GLIS3 gene on chromosome 9p24.2 (OMIM 610192) mutations were amplified by polymerase chain reaction (PCR) and sequenced directly

Summary

Introduction

Mutations in the GLI-similar 3 (GLIS3) gene encoding the transcription factor GLIS3 are a rare cause of neonatal diabetes and congenital hypothyroidism with 12 reported patients to date. Case presentation: We report a new case for consanguineous parents with homozygous novel mutation in GLIS3 gene who presented with neonatal diabetes mellitus, severe resistant congenital hypothyroidism, cholestatic liver disease, bilateral congenital glaucoma and facial dysmorphism. The Gli-similar family of Kruppel-like zinc finger proteins is comprised of three proteins, Glis. GLI-similar 3 (GLIS3) is identified transcription factor containing five Kruppel-like zinc finger motifs [5]. GLIS3 expression occurs early in embryogenesis and is thought to play a critical role in the cellular regulation of development by functioning as a repressor or activator of Alghamdi et al BMC Endocrine Disorders (2017) 17:14 resulted in severely affected patient with an extended phenotype including abnormalities in external genitalia that have not been previously described

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