Hyperinsulinemic hypoglycemia in a patient with an intragenic NSD1 mutation

Salas, Pilar Carrasco; Milla, Carmen Palma; Rosales, Jose Miguel Lezana; Benito, Carmen; Freire, Sara Franco; Siles, Juan López

doi:10.1002/ajmg.a.37440

Cited by 5 publications

(7 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Matsuo et al did indeed speculate that NSD1 may be associated with beta cell‐specific transcription factors that suppress the expression of insulin, and that NSD1 haploinsufficiency may cause excessive expression of insulin [Matsuo et al, 2013]; however, they were not able to exclude the possibility that another gene in the 5q35 region was the cause of HI. These patients, along with an additional patient described by Carrasco Salas et al (), support the hypothesis that haploinsufficiency of NSD1 results in dysregulated insulin expression.…”

Section: Discussionsupporting

confidence: 74%

“…Although hypoglycemia has been described as a minor feature in Sotos syndrome, there are a few publications regarding genotype–phenotype correlations. Recently, data have been published on eight individuals with HI and Sotos syndrome, with 7/8 patients having a 5q35 microdeletion and 8/8 patients having transient neonatal HI, with 3/8 requiring diazoxide treatment [Matsuo et al, ; Carrasco Salas et al, ; Nakamura et al, ]. In our cohort, at least 3/7 patients (Patient 1, Patient 4, and Patient 6) had persistent HI, a clinical feature not previously reported in the Sotos syndrome literature, with HI being present beyond 1 year of life.…”

Section: Discussionsupporting

confidence: 60%

“…More recently, Nakamura et al reported an additional patient with a 5q35 deletion and transient neonatal HI [Nakamura et al, ]. Carrasco salas et al first described a patient with an intragenic NSD1 mutation and transient HI [Carrasco Salas, et al, ]. A majority of the cases reported to date of Sotos syndrome and HI have been the result of microdeletions of NSD1 (7/8) and all have been transient (8/8).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hyperinsulinemic hypoglycemia in seven patients with de novo NSD1 mutations

Grand

Gonzalez-Gandolfi

Ackermann

et al. 2019

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Sotos syndrome is an overgrowth syndrome characterized by distinctive facial features and intellectual disability caused by haploinsufficiency of the NSD1 gene. Genotype-phenotype correlations have been observed, with major anomalies seen more frequently in patients with 5q35 deletions than those with point mutations in NSD1. Though endocrine features have rarely been described, transient hyperinsulinemic hypoglycemia (HI) of the neonatal period has been reported as an uncommon presentation of Sotos syndrome. Eight cases of 5q35 deletions and one patient with an intragenic NSD1 mutation with transient HI have been reported. Here, we describe seven individuals with HI caused by NSD1 gene mutations with three having persistent hyperinsulinemic hypoglycemia. These patients with persistent HI and Sotos syndrome caused by NSD1 mutations, further dispel the hypothesis that HI is due to the deletion of other genes in the deleted 5q35 region. These patients emphasize that NSD1 haploinsufficiency is sufficient to cause HI, and suggest that Sotos syndrome should be considered in patients presenting with neonatal HI. Lastly, these patients help extend the phenotypic spectrum of Sotos syndrome to include HI as a significant feature. K E Y W O R D S hyperinsulinism, hypoglycemia, NSD1, overgrowth syndrome, sacrococcygeal teratoma, Sotos syndrome

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Discussionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hyperinsulinemic hypoglycemia in seven patients with de novo NSD1 mutations

Grand

Gonzalez-Gandolfi

Ackermann

et al. 2019

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“… 4 MAGEL2 is an imprinted gene, loss-of-function mutations only cause disease when present on the paternal allele. 5 Intergenic mutations affecting NSD1 have been reported; these would not be detected by exome sequencing ( 55 ). …”

Section: Genetic Types Of Congenital Hyperinsulinismmentioning

confidence: 99%

“… 5 Intergenic mutations affecting NSD1 have been reported; these would not be detected by exome sequencing ( 55 ). …”

Section: Genetic Types Of Congenital Hyperinsulinismmentioning

confidence: 99%

Congenital Hyperinsulinism: Current Laboratory-Based Approaches to the Genetic Diagnosis of a Heterogeneous Disease

2022

View full text Add to dashboard Cite

Congenital hyperinsulinism is characterised by the inappropriate release of insulin during hypoglycaemia. This potentially life-threatening disorder can occur in isolation, or present as a feature of syndromic disease. Establishing the underlying aetiology of the hyperinsulinism is critical for guiding medical management of this condition especially in children with diazoxide-unresponsive hyperinsulinism where the underlying genetics determines whether focal or diffuse pancreatic disease is present. Disease-causing single nucleotide variants affecting over 30 genes are known to cause persistent hyperinsulinism with mutations in the KATP channel genes (ABCC8 and KCNJ11) most commonly identified in children with severe persistent disease. Defects in methylation, changes in chromosome number, and large deletions and duplications disrupting multiple genes are also well described in congenital hyperinsulinism, further highlighting the genetic heterogeneity of this condition. Next-generation sequencing has revolutionised the approach to genetic testing for congenital hyperinsulinism with targeted gene panels, exome, and genome sequencing being highly sensitive methods for the analysis of multiple disease genes in a single reaction. It should though be recognised that limitations remain with next-generation sequencing with no single application able to detect all reported forms of genetic variation. This is an important consideration for hyperinsulinism genetic testing as comprehensive screening may require multiple investigations.

show abstract

Syndromic Causes of Congenital Hyperinsulinism

Kalish

Arnoux

2019

Congenital Hyperinsulinism

View full text Add to dashboard Cite

Hyperinsulinemic hypoglycemia in a patient with an intragenic NSD1 mutation

Cited by 5 publications

References 9 publications

Hyperinsulinemic hypoglycemia in seven patients with de novo NSD1 mutations

Hyperinsulinemic hypoglycemia in seven patients with de novo NSD1 mutations

Congenital Hyperinsulinism: Current Laboratory-Based Approaches to the Genetic Diagnosis of a Heterogeneous Disease

Syndromic Causes of Congenital Hyperinsulinism

Contact Info

Product

Resources

About