Bilateral cataracts in a 6-yr-old with new onset diabetes: a novel presentation of a known<i>INS</i>gene mutation

Wasserman, Halley; Hufnagel, Robert B.; Utz, Virginia Miraldi; Zhang, Kejian; Valencia, C. Alexander; Leslie, Nancy; Crimmins, Nancy A.

doi:10.1111/pedi.12335

Cited by 13 publications

(13 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An animal study by Renner et al [ 12 ] demonstrated that cataracts appeared earlier in pigs with an insulin gene mutation (C94Y), and progressed with age. In addition, Wasserman et al [ 13 ] described a case of insulin gene mutations similar to our case, in that the patient suffered from bilateral cataracts. Lenfant et al [ 14 ] reported that a 6-year-old girl had a heterozygous p.R825Q ABCC8 mutation that was responsible for her diabetes and a homozygous p.G71S mutation in CRYBB1 that was responsible for her congenital cataract, suggesting that double-gene mutations may contribute to the clinical manifestation of diabetic cataracts as well.…”

Section: Discussionsupporting

confidence: 77%

Bilateral cataracts as the first manifestation of type 1 diabetes mellitus

Zeng²,

Xuan³

et al. 2018

Medicine

View full text Add to dashboard Cite

Rationale:Cataracts can occur in children and adolescents with Type 1 Diabetes Mellitus who have poorly controlled glycemia. Here, we report a case of a 16-year-old female, who was diagnosed with bilateral cataracts, and genetic screening identified a mutation in the PRRC2A gene which is rarely reported. After surgery, retinopathy was found in this patient, combined with the published literature, we encourage that postoperative monitoring for retinal lesions during the follow-up visits should be conducted.Patient concerns:In this article, we present an adolescent diagnosed with bilateral cataracts, and developed retinopathy during the follow-up visits. Genetic screening identified a mutation in the PRRC2A gene.Diagnoses:The diagnoses of Diabetic cataracts, Type 1 diabetes and Diabetic retinopathy was made.Interventions:The patient underwent surgery in both eyes, and hypoglycemic treatment was provided.Outcomes:The surgery achieved satisfactory results, during the follow-up visits, her visual acuity was reported as 0.8 in the right eye and 1.0 in the left eye. Besides, her blood glucose was well controlled, and her glycated hemoglobin was reduced to 6.9% after three months of continuous treatment.Lessons:This case highlights the importance of genetic screening for detecting mutations in diabetes-related genes, and postoperative monitoring for retinal lesions during the follow-up visits.

show abstract

Section: Discussionsupporting

confidence: 77%

Bilateral cataracts as the first manifestation of type 1 diabetes mellitus

Zeng²,

Xuan³

et al. 2018

Medicine

View full text Add to dashboard Cite

show abstract

“…There are few other clinical features associated with INS gene mutations other than the direct role of insulin on fetal growth and postnatal glucose. Premature development of cataract is a feature of the Munich pig (C95S) and this has also been reported in a minority of patients with dominant INS gene mutations [ 33 , 41 ].…”

Section: Clinical Characteristics and Treatment Of Patients With Ins Gene Mutationsmentioning

confidence: 99%

In celebration of a century with insulin – Update of insulin gene mutations in diabetes

Støy

Franco

et al. 2021

Molecular Metabolism

View full text Add to dashboard Cite

Background While insulin has been central to the pathophysiology and treatment of patients with diabetes for the last 100 years, it has only been since 2007 that genetic variation in the INS gene has been recognised as a major cause of monogenic diabetes. Both dominant and recessive mutations in the INS gene are now recognised as important causes of neonatal diabetes and offer important insights into both the structure and function of insulin. It is also recognised that in rare cases, mutations in the INS gene can be found in patients with diabetes diagnosed outside the first year of life. Scope of Review This review examines the genetics and clinical features of monogenic diabetes resulting from INS gene mutations from the first description in 2007 and includes information from 389 patients from 292 families diagnosed in Exeter with INS gene mutations. We discuss the implications for diagnosing and treating this subtype of monogenic diabetes. Major Conclusions The dominant mutations in the INS gene typically affect the secondary structure of the insulin protein, usually by disrupting the 3 disulfide bonds in mature insulin. The resulting misfolded protein results in ER stress and beta-cell destruction. In contrast, recessive INS gene mutations typically result in no functional protein being produced due to reduced insulin biosynthesis or loss-of-function mutations in the insulin protein. There are clinical differences between the two genetic aetiologies, between the specific mutations, and within patients with identical mutations.

show abstract

“…The indication for MODY gene testing in this patient was the early onset bilateral cataracts. There are no published data on the prevalence of cataracts in monogenic diabetes, but mutations in INS and HNF1B genes have been found to be associated with acquired cataracts . We highlighted that diabetes associated with extrapancreatic features were also an important indicator for MODY genetic screening.…”

Section: Discussionmentioning

confidence: 90%

Molecular diagnosis of maturity‐onset diabetes of the young in a cohort of Chinese children

Lin

Sheng

et al. 2020

Pediatr Diabetes

View full text Add to dashboard Cite

Objective: The purpose of this study was to investigate the molecular basis of maturity-onset diabetes of the young (MODY) by whole-exome sequencing (WES) and estimate the frequency and describe the clinical characteristics of MODY in southern China. Methods: Genetic analysis was performed in 42 patients with MODY aged 1 month to 18 years among a cohort of 759 patients with diabetes, identified with the following four clinical criteria: age of diagnosis ≤18 years; negative pancreatic autoantibodies; family history of diabetes; or persistently detectable C-peptide; or diabetes associated with extrapancreatic features. GCK gene mutations were first screened by Sanger sequencing. GCK mutation-negative patients were further analyzed by WES. Results: Mutations were identified in 24 patients: 20 mutations in GCK, 1 in HNF4A, 1 in INS, 1 in ABCC8, and a 17q12 microdeletion. Four previously unpublished novel GCK mutations: c.1108G>C in exon 9, and c.1339C>T, c.1288_1290delCTG, and c.1340_1343delGGGGinsCTGGTCT in exon 10 were detected. WES identified a novel missense mutation c.311A>G in exon 3 in the INS gene, and copy number variation analysis detected a 1.4 Mb microdeletion in the long arm of the chromosome 17q12 region. Compared with mutation-negative subjects, the mutation-positive subjects had lower hemoglobin A1c and initial blood glucose levels. Conclusions: Most MODY cases in this study were due to GCK mutations, which is in contrast to previous reports in Chinese patients. Diabetes associated with extrapancreatic features should be a clinical criterion for MODY genetic analysis. Mutational analysis by WES provided a precise diagnosis of MODY subtypes. Moreover, WES can be useful for detecting large deletions in coding regions in addition to point mutations. K E Y W O R D S childhood, maturity-onset diabetes of the young, South China, whole-exome sequencing Aijing Xu and Yunting Lin contribute equally to this work.

show abstract

Bilateral cataracts in a 6-yr-old with new onset diabetes: a novel presentation of a knownINSgene mutation

Cited by 13 publications

References 21 publications

Bilateral cataracts as the first manifestation of type 1 diabetes mellitus

Bilateral cataracts as the first manifestation of type 1 diabetes mellitus

In celebration of a century with insulin – Update of insulin gene mutations in diabetes

Molecular diagnosis of maturity‐onset diabetes of the young in a cohort of Chinese children

Contact Info

Product

Resources

About