Novel exostosin-2 missense variants in a family with autosomal recessive exostosin-2-related syndrome

further evidences on the phenotype

Mattia Gentile, Emanuele Agolini, Dario Cocciadiferro, Romina Ficarella, Emanuela Ponzi, Emanuele Bellacchio, Maria F Antonucci, Antonio Novelli

Research output: Contribution to journalArticle

Abstract

Biallelic exostosin-2 (EXT2) pathogenic variants have been described as the cause of the Seizures-Scoliosis-Macrocephaly syndrome (OMIM 616682) characterized by intellectual disability, facial dysmorphisms and seizures. More recently, it has been proposed to rename this disorder with the acronym AREXT2 (autosomal recessive EXT2-related syndrome). Here, we report the third family affected by AREXT2 syndrome, harboring compound missense variants in EXT2, p.Asp227Asn, and p.Tyr608Cys. In addition, our patients developed multiple exostoses, which were not observed in the previously described families. AREXT2 syndrome can be considered as a multiorgan Congenital Disorder of Glycosylation caused by a significant, but non-lethal, decrease in EXT2 expression, thereby affecting the synthesis of the heparan sulfate proteoglycans, which is relevant in many physiological processes. Our finding expands the clinical and molecular spectrum of the AREXT2 syndrome and suggests a possible genotype/phenotype correlation in the development of the exostoses.

Original languageEnglish
JournalClinical Genetics
DOIs
Publication statusE-pub ahead of print - Oct 4 2018

Fingerprint

Phenotype
Seizures
Congenital Disorders of Glycosylation
Multiple Hereditary Exostoses
Megalencephaly
Exostoses
Physiological Phenomena
Genetic Databases
Heparan Sulfate Proteoglycans
exostosin-2
Genetic Association Studies
Scoliosis
Intellectual Disability

Cite this

Novel exostosin-2 missense variants in a family with autosomal recessive exostosin-2-related syndrome : further evidences on the phenotype. / Gentile, Mattia; Agolini, Emanuele; Cocciadiferro, Dario; Ficarella, Romina; Ponzi, Emanuela; Bellacchio, Emanuele; Antonucci, Maria F; Novelli, Antonio.

In: Clinical Genetics, 04.10.2018.

Research output: Contribution to journalArticle

Gentile, Mattia ; Agolini, Emanuele ; Cocciadiferro, Dario ; Ficarella, Romina ; Ponzi, Emanuela ; Bellacchio, Emanuele ; Antonucci, Maria F ; Novelli, Antonio. / Novel exostosin-2 missense variants in a family with autosomal recessive exostosin-2-related syndrome : further evidences on the phenotype. In: Clinical Genetics. 2018.
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abstract = "Biallelic exostosin-2 (EXT2) pathogenic variants have been described as the cause of the Seizures-Scoliosis-Macrocephaly syndrome (OMIM 616682) characterized by intellectual disability, facial dysmorphisms and seizures. More recently, it has been proposed to rename this disorder with the acronym AREXT2 (autosomal recessive EXT2-related syndrome). Here, we report the third family affected by AREXT2 syndrome, harboring compound missense variants in EXT2, p.Asp227Asn, and p.Tyr608Cys. In addition, our patients developed multiple exostoses, which were not observed in the previously described families. AREXT2 syndrome can be considered as a multiorgan Congenital Disorder of Glycosylation caused by a significant, but non-lethal, decrease in EXT2 expression, thereby affecting the synthesis of the heparan sulfate proteoglycans, which is relevant in many physiological processes. Our finding expands the clinical and molecular spectrum of the AREXT2 syndrome and suggests a possible genotype/phenotype correlation in the development of the exostoses.",
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AU - Cocciadiferro, Dario

AU - Ficarella, Romina

AU - Ponzi, Emanuela

AU - Bellacchio, Emanuele

AU - Antonucci, Maria F

AU - Novelli, Antonio

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