Dataset Information

Homozygous Missense Variants in NTNG2, Encoding a Presynaptic Netrin-G2 Adhesion Protein, Lead to a Distinct Neurodevelopmental Disorder.

ABSTRACT: NTNG2 encodes netrin-G2, a membrane-anchored protein implicated in the molecular organization of neuronal circuitry and synaptic organization and diversification in vertebrates. In this study, through a combination of exome sequencing and autozygosity mapping, we have identified 16 individuals (from seven unrelated families) with ultra-rare homozygous missense variants in NTNG2; these individuals present with shared features of a neurodevelopmental disorder consisting of global developmental delay, severe to profound intellectual disability, muscle weakness and abnormal tone, autistic features, behavioral abnormalities, and variable dysmorphisms. The variants disrupt highly conserved residues across the protein. Functional experiments, including in silico analysis of the protein structure, in vitro assessment of cell surface expression, and in vitro knockdown, revealed potential mechanisms of pathogenicity of the variants, including loss of protein function and decreased neurite outgrowth. Our data indicate that appropriate expression of NTNG2 plays an important role in neurotypical development.

SUBMITTER: Dias CM

PROVIDER: S-EPMC6849109 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Homozygous Missense Variants in NTNG2, Encoding a Presynaptic Netrin-G2 Adhesion Protein, Lead to a Distinct Neurodevelopmental Disorder.

Dias Caroline M CM Punetha Jaya J Zheng Céline C Mazaheri Neda N Rad Abolfazl A Efthymiou Stephanie S Petersen Andrea A Dehghani Mohammadreza M Pehlivan Davut D Partlow Jennifer N JN Posey Jennifer E JE Salpietro Vincenzo V Gezdirici Alper A Malamiri Reza Azizi RA Al Menabawy Nihal M NM Selim Laila A LA Vahidi Mehrjardi Mohammad Yahya MY Banu Selina S Polla Daniel L DL Yang Edward E Rezazadeh Varaghchi Jamileh J Mitani Tadahiro T van Beusekom Ellen E Najafi Maryam M Sedaghat Alireza A Keller-Ramey Jennifer J Durham Leslie L Coban-Akdemir Zeynep Z Karaca Ender E Orlova Valeria V Schaeken Lieke L M LLM Sherafat Amir A Jhangiani Shalini N SN Stanley Valentina V Shariati Gholamreza G Galehdari Hamid H Gleeson Joseph G JG Walsh Christopher A CA Lupski James R JR Seiradake Elena E Houlden Henry H van Bokhoven Hans H Maroofian Reza R

American journal of human genetics 20191024 5

NTNG2 encodes netrin-G2, a membrane-anchored protein implicated in the molecular organization of neuronal circuitry and synaptic organization and diversification in vertebrates. In this study, through a combination of exome sequencing and autozygosity mapping, we have identified 16 individuals (from seven unrelated families) with ultra-rare homozygous missense variants in NTNG2; these individuals present with shared features of a neurodevelopmental disorder consisting of global developmental del ...[more]

PMID: 31668703

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Dataset Information

Homozygous Missense Variants in NTNG2, Encoding a Presynaptic Netrin-G2 Adhesion Protein, Lead to a Distinct Neurodevelopmental Disorder.

Publications

Homozygous Missense Variants in NTNG2, Encoding a Presynaptic Netrin-G2 Adhesion Protein, Lead to a Distinct Neurodevelopmental Disorder.

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