Uniparental isodisomy of chromosome 1 results in glycogen storage disease type III with profound growth retardation

Emanuela Ponzi, Viola Alesi, Francesca R Lepri, Silvia Genovese, Sara Loddo, Mafalda Mucciolo, Antonio Novelli, Carlo Dionisi-Vici, Arianna Maiorana

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Glycogen storage disease type III (GSDIII) is caused by mutations of AGL gene with debranching enzyme deficiency. Patients with GSDIII manifest fasting hypoglycemia, hepatomegaly, hepatopathy, myopathy, and cardiomyopathy. We report on an 18-year-old boy with a profound growth retardation (<3 SD) besides typical clinical features of GSDIII, whereby endocrinological studies were negative.

METHODS AND RESULTS: Molecular analysis of AGL gene revealed the homozygous reported variant c.3903_3904insA. Since discordant results from segregation studies showed the carrier status in one parent only, SNP array and short tandem repeats analyses were performed, revealing a paternal disomy of chromosome 1 (UPD1).

CONCLUSION: This study describes the first case of GSDIII resulting from UPD1. UPD can play an important role even in case of imprinted genes. DIRAS3 is a maternally imprinted tumor suppressor gene, located on chromosome 1p31, and implicated in growth and oncogenesis. It can be speculated that DIRAS3 overexpression might have a role in the severe short stature of our patient. The study emphasizes the importance of parental segregation analysis especially in patients with recessive conditions to look for specific genetic causes of disease and to estimate properly the risk of family recurrence.

Original languageEnglish
Pages (from-to)e634
JournalMolecular genetics & genomic medicine
DOIs
Publication statusE-pub ahead of print - Mar 27 2019

Fingerprint

Glycogen Storage Disease Type III
Uniparental Disomy
Chromosomes, Human, Pair 1
Growth
Genes
Inborn Genetic Diseases
Hepatomegaly
Muscular Diseases
Tumor Suppressor Genes
Cardiomyopathies
Hypoglycemia
Microsatellite Repeats
Single Nucleotide Polymorphism
Carcinogenesis
Chromosomes
Recurrence
Mutation
Enzymes

Cite this

Uniparental isodisomy of chromosome 1 results in glycogen storage disease type III with profound growth retardation. / Ponzi, Emanuela; Alesi, Viola; Lepri, Francesca R; Genovese, Silvia; Loddo, Sara; Mucciolo, Mafalda; Novelli, Antonio; Dionisi-Vici, Carlo; Maiorana, Arianna.

In: Molecular genetics & genomic medicine, 27.03.2019, p. e634.

Research output: Contribution to journalArticle

@article{32eb6abf1b8f4b29a89713c80fde49bd,
title = "Uniparental isodisomy of chromosome 1 results in glycogen storage disease type III with profound growth retardation",
abstract = "BACKGROUND: Glycogen storage disease type III (GSDIII) is caused by mutations of AGL gene with debranching enzyme deficiency. Patients with GSDIII manifest fasting hypoglycemia, hepatomegaly, hepatopathy, myopathy, and cardiomyopathy. We report on an 18-year-old boy with a profound growth retardation (<3 SD) besides typical clinical features of GSDIII, whereby endocrinological studies were negative.METHODS AND RESULTS: Molecular analysis of AGL gene revealed the homozygous reported variant c.3903_3904insA. Since discordant results from segregation studies showed the carrier status in one parent only, SNP array and short tandem repeats analyses were performed, revealing a paternal disomy of chromosome 1 (UPD1).CONCLUSION: This study describes the first case of GSDIII resulting from UPD1. UPD can play an important role even in case of imprinted genes. DIRAS3 is a maternally imprinted tumor suppressor gene, located on chromosome 1p31, and implicated in growth and oncogenesis. It can be speculated that DIRAS3 overexpression might have a role in the severe short stature of our patient. The study emphasizes the importance of parental segregation analysis especially in patients with recessive conditions to look for specific genetic causes of disease and to estimate properly the risk of family recurrence.",
author = "Emanuela Ponzi and Viola Alesi and Lepri, {Francesca R} and Silvia Genovese and Sara Loddo and Mafalda Mucciolo and Antonio Novelli and Carlo Dionisi-Vici and Arianna Maiorana",
note = "{\circledC} 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.",
year = "2019",
month = "3",
day = "27",
doi = "10.1002/mgg3.634",
language = "English",
pages = "e634",
journal = "Molecular genetics & genomic medicine",
issn = "2324-9269",
publisher = "John Wiley and Sons Inc.",

}

TY - JOUR

T1 - Uniparental isodisomy of chromosome 1 results in glycogen storage disease type III with profound growth retardation

AU - Ponzi, Emanuela

AU - Alesi, Viola

AU - Lepri, Francesca R

AU - Genovese, Silvia

AU - Loddo, Sara

AU - Mucciolo, Mafalda

AU - Novelli, Antonio

AU - Dionisi-Vici, Carlo

AU - Maiorana, Arianna

N1 - © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

PY - 2019/3/27

Y1 - 2019/3/27

N2 - BACKGROUND: Glycogen storage disease type III (GSDIII) is caused by mutations of AGL gene with debranching enzyme deficiency. Patients with GSDIII manifest fasting hypoglycemia, hepatomegaly, hepatopathy, myopathy, and cardiomyopathy. We report on an 18-year-old boy with a profound growth retardation (<3 SD) besides typical clinical features of GSDIII, whereby endocrinological studies were negative.METHODS AND RESULTS: Molecular analysis of AGL gene revealed the homozygous reported variant c.3903_3904insA. Since discordant results from segregation studies showed the carrier status in one parent only, SNP array and short tandem repeats analyses were performed, revealing a paternal disomy of chromosome 1 (UPD1).CONCLUSION: This study describes the first case of GSDIII resulting from UPD1. UPD can play an important role even in case of imprinted genes. DIRAS3 is a maternally imprinted tumor suppressor gene, located on chromosome 1p31, and implicated in growth and oncogenesis. It can be speculated that DIRAS3 overexpression might have a role in the severe short stature of our patient. The study emphasizes the importance of parental segregation analysis especially in patients with recessive conditions to look for specific genetic causes of disease and to estimate properly the risk of family recurrence.

AB - BACKGROUND: Glycogen storage disease type III (GSDIII) is caused by mutations of AGL gene with debranching enzyme deficiency. Patients with GSDIII manifest fasting hypoglycemia, hepatomegaly, hepatopathy, myopathy, and cardiomyopathy. We report on an 18-year-old boy with a profound growth retardation (<3 SD) besides typical clinical features of GSDIII, whereby endocrinological studies were negative.METHODS AND RESULTS: Molecular analysis of AGL gene revealed the homozygous reported variant c.3903_3904insA. Since discordant results from segregation studies showed the carrier status in one parent only, SNP array and short tandem repeats analyses were performed, revealing a paternal disomy of chromosome 1 (UPD1).CONCLUSION: This study describes the first case of GSDIII resulting from UPD1. UPD can play an important role even in case of imprinted genes. DIRAS3 is a maternally imprinted tumor suppressor gene, located on chromosome 1p31, and implicated in growth and oncogenesis. It can be speculated that DIRAS3 overexpression might have a role in the severe short stature of our patient. The study emphasizes the importance of parental segregation analysis especially in patients with recessive conditions to look for specific genetic causes of disease and to estimate properly the risk of family recurrence.

U2 - 10.1002/mgg3.634

DO - 10.1002/mgg3.634

M3 - Article

SP - e634

JO - Molecular genetics & genomic medicine

JF - Molecular genetics & genomic medicine

SN - 2324-9269

ER -