Case reports of juvenile GM1 gangliosidosisis type II caused by mutation in GLB1 gene

Parvaneh Karimzadeh, Samaneh Naderi, Farzaneh Modarresi, Hassan Dastsooz, Hamid Nemati, Tayebeh Farokhashtiani, Bibi Shahin Shamsian, Soroor Inaloo, Mohammad A Faghihi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Type II or juvenile GM1-gangliosidosis is an autosomal recessive lysosomal storage disorder, which is clinically distinct from infantile form of the disease by the lack of characteristic cherry-red spot and hepatosplenomegaly. The disease is characterized by slowly progressive neurodegeneration and mild skeletal changes. Due to the later age of onset and uncharacteristic presentation, diagnosis is frequently puzzled with other ataxic and purely neurological disorders. Up to now, 3-4 types of GM1-gangliosidosis have been reported and among them type I is the most common phenotype with the age of onset around 6 months. Various forms of GM1-gangliosidosis are caused by GLB1 gene mutations but severity of the disease and age of onset are directly related to the position and the nature of deleterious mutations. However, due to its unique genetic cause and overlapping clinical features, some researchers believe that GM1 gangliosidosis represents an overlapped disease spectrum instead of four distinct types. Case presentation: Here, we report a less frequent type of autosomal recessive GM1 gangliosidosis with perplexing clinical presentation in three families in the southwest part of Iran, who are unrelated but all from "Lurs" ethnic background. To identify disease-causing mutations, Whole Exome Sequencing (WES) utilizing next generation sequencing was performed. Four patients from three families were investigated with the age of onset around 3 years old. Clinical presentations were ataxia, gate disturbances and dystonia leading to wheelchair-dependent disability, regression of intellectual abilities, and general developmental regression. They all were born in consanguineous families with no previous documented similar disease in their parents. A homozygote missense mutation in GLB1 gene (c. 601 G > A, p.R201C) was found in all patients. Using Sanger sequencing this identified mutation was confirmed in the proband, their parents, grandparents, and extended family members, confirming its autosomal recessive pattern of inheritance. Conclusions: Our study identified a rare pathogenic missense mutation in GLB1 gene in patients with complex neurodevelopmental findings, which can extend the list of differential diagnoses for childhood ataxia in Iranian patients.

Original languageEnglish (US)
Article number73
JournalBMC Medical Genetics
Volume18
Issue number1
DOIs
StatePublished - Jul 17 2017

Fingerprint

GM1 Gangliosidosis
Age of Onset
Mutation
Genes
Missense Mutation
Ataxia
Parents
Exome
Inheritance Patterns
Wheelchairs
Aptitude
Dystonia
Homozygote
Iran
Nervous System Diseases
Intellectual Disability
Differential Diagnosis
Research Personnel
Phenotype

Keywords

  • Case report
  • GLB1
  • GM1 gangliosidosis

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Karimzadeh, P., Naderi, S., Modarresi, F., Dastsooz, H., Nemati, H., Farokhashtiani, T., ... Faghihi, M. A. (2017). Case reports of juvenile GM1 gangliosidosisis type II caused by mutation in GLB1 gene. BMC Medical Genetics, 18(1), [73]. https://doi.org/10.1186/s12881-017-0417-4

Case reports of juvenile GM1 gangliosidosisis type II caused by mutation in GLB1 gene. / Karimzadeh, Parvaneh; Naderi, Samaneh; Modarresi, Farzaneh; Dastsooz, Hassan; Nemati, Hamid; Farokhashtiani, Tayebeh; Shamsian, Bibi Shahin; Inaloo, Soroor; Faghihi, Mohammad A.

In: BMC Medical Genetics, Vol. 18, No. 1, 73, 17.07.2017.

Research output: Contribution to journalArticle

Karimzadeh, P, Naderi, S, Modarresi, F, Dastsooz, H, Nemati, H, Farokhashtiani, T, Shamsian, BS, Inaloo, S & Faghihi, MA 2017, 'Case reports of juvenile GM1 gangliosidosisis type II caused by mutation in GLB1 gene', BMC Medical Genetics, vol. 18, no. 1, 73. https://doi.org/10.1186/s12881-017-0417-4
Karimzadeh P, Naderi S, Modarresi F, Dastsooz H, Nemati H, Farokhashtiani T et al. Case reports of juvenile GM1 gangliosidosisis type II caused by mutation in GLB1 gene. BMC Medical Genetics. 2017 Jul 17;18(1). 73. https://doi.org/10.1186/s12881-017-0417-4
Karimzadeh, Parvaneh ; Naderi, Samaneh ; Modarresi, Farzaneh ; Dastsooz, Hassan ; Nemati, Hamid ; Farokhashtiani, Tayebeh ; Shamsian, Bibi Shahin ; Inaloo, Soroor ; Faghihi, Mohammad A. / Case reports of juvenile GM1 gangliosidosisis type II caused by mutation in GLB1 gene. In: BMC Medical Genetics. 2017 ; Vol. 18, No. 1.
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N2 - Background: Type II or juvenile GM1-gangliosidosis is an autosomal recessive lysosomal storage disorder, which is clinically distinct from infantile form of the disease by the lack of characteristic cherry-red spot and hepatosplenomegaly. The disease is characterized by slowly progressive neurodegeneration and mild skeletal changes. Due to the later age of onset and uncharacteristic presentation, diagnosis is frequently puzzled with other ataxic and purely neurological disorders. Up to now, 3-4 types of GM1-gangliosidosis have been reported and among them type I is the most common phenotype with the age of onset around 6 months. Various forms of GM1-gangliosidosis are caused by GLB1 gene mutations but severity of the disease and age of onset are directly related to the position and the nature of deleterious mutations. However, due to its unique genetic cause and overlapping clinical features, some researchers believe that GM1 gangliosidosis represents an overlapped disease spectrum instead of four distinct types. Case presentation: Here, we report a less frequent type of autosomal recessive GM1 gangliosidosis with perplexing clinical presentation in three families in the southwest part of Iran, who are unrelated but all from "Lurs" ethnic background. To identify disease-causing mutations, Whole Exome Sequencing (WES) utilizing next generation sequencing was performed. Four patients from three families were investigated with the age of onset around 3 years old. Clinical presentations were ataxia, gate disturbances and dystonia leading to wheelchair-dependent disability, regression of intellectual abilities, and general developmental regression. They all were born in consanguineous families with no previous documented similar disease in their parents. A homozygote missense mutation in GLB1 gene (c. 601 G > A, p.R201C) was found in all patients. Using Sanger sequencing this identified mutation was confirmed in the proband, their parents, grandparents, and extended family members, confirming its autosomal recessive pattern of inheritance. Conclusions: Our study identified a rare pathogenic missense mutation in GLB1 gene in patients with complex neurodevelopmental findings, which can extend the list of differential diagnoses for childhood ataxia in Iranian patients.

AB - Background: Type II or juvenile GM1-gangliosidosis is an autosomal recessive lysosomal storage disorder, which is clinically distinct from infantile form of the disease by the lack of characteristic cherry-red spot and hepatosplenomegaly. The disease is characterized by slowly progressive neurodegeneration and mild skeletal changes. Due to the later age of onset and uncharacteristic presentation, diagnosis is frequently puzzled with other ataxic and purely neurological disorders. Up to now, 3-4 types of GM1-gangliosidosis have been reported and among them type I is the most common phenotype with the age of onset around 6 months. Various forms of GM1-gangliosidosis are caused by GLB1 gene mutations but severity of the disease and age of onset are directly related to the position and the nature of deleterious mutations. However, due to its unique genetic cause and overlapping clinical features, some researchers believe that GM1 gangliosidosis represents an overlapped disease spectrum instead of four distinct types. Case presentation: Here, we report a less frequent type of autosomal recessive GM1 gangliosidosis with perplexing clinical presentation in three families in the southwest part of Iran, who are unrelated but all from "Lurs" ethnic background. To identify disease-causing mutations, Whole Exome Sequencing (WES) utilizing next generation sequencing was performed. Four patients from three families were investigated with the age of onset around 3 years old. Clinical presentations were ataxia, gate disturbances and dystonia leading to wheelchair-dependent disability, regression of intellectual abilities, and general developmental regression. They all were born in consanguineous families with no previous documented similar disease in their parents. A homozygote missense mutation in GLB1 gene (c. 601 G > A, p.R201C) was found in all patients. Using Sanger sequencing this identified mutation was confirmed in the proband, their parents, grandparents, and extended family members, confirming its autosomal recessive pattern of inheritance. Conclusions: Our study identified a rare pathogenic missense mutation in GLB1 gene in patients with complex neurodevelopmental findings, which can extend the list of differential diagnoses for childhood ataxia in Iranian patients.

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