biostudies-literatureKurolap ANHGRI NIH HHSNINDS NIH HHS518-532https://www.ebi.ac.uk/biostudies/studies/S-EPMC8948158biostudies-literatureUnknown109(3)Cell adhesion molecules are membrane-bound proteins predominantly expressed in the central nervous system along principal axonal pathways with key roles in nervous system development, neural cell differentiation and migration, axonal growth and guidance, myelination, and synapse formation. Here, we describe ten affected individuals with bi-allelic variants in the neuronal cell adhesion molecule NRCAM that lead to a neurodevelopmental syndrome of varying severity; the individuals are from eight families. This syndrome is characterized by developmental delay/intellectual disability, hypotonia, peripheral neuropathy, and/or spasticity. Computational analyses of NRCAM variants, many of which cluster in the third fibronectin type III (Fn-III) domain, strongly suggest a deleterious effect on NRCAmerican journal of human geneticsBi-allelic variants in neuronal cell adhesion molecule cause a neurodevelopmental disorder characterized by developmental delay, hypotonia, neuropathy/spasticity.PMC8948158U01 HG007672R01 NS106298Gonzaga-Jauregui CRice JAst GUndiagnosed Diseases Networkvan Eyk CLMah JKAtkinson DTammer LShashi VWang HKaslin JCope HCandayan ABakhtiari SJordanova AKurolap ASency VGlaser FXin BSullivan JALeibu RKreuder FParman YElpeleg OIlivitzki AHarel TBattaloglu EInnes AMKocasoy-Orhan EDuvdevani MPColquhoun DKruer MCBaris Feldman HSoudry SDouek AMFahey MCGecz JMeiner VHenry JWlodkowic DfalseBi-allelic variants in neuronal cell adhesion molecule cause a neurodevelopmental disorder characterized by developmental delay, hypotonia, neuropathy/spasticity.Cell adhesion molecules are membrane-bound proteins predominantly expressed in the central nervous system along principal axonal pathways with key roles in nervous system development, neural cell differentiation and migration, axonal growth and guidance, myelination, and synapse formation. Here, we describe ten affected individuals with bi-allelic variants in the neuronal cell adhesion molecule NRCAM that lead to a neurodevelopmental syndrome of varying severity; the individuals are from eight families. This syndrome is characterized by developmental delay/intellectual disability, hypotonia, peripheral neuropathy, and/or spasticity. Computational analyses of NRCAM variants, many of which cluster in the third fibronectin type III (Fn-III) domain, strongly suggest a deleterious effect on NRC2022-01-01T00:00:00Z2022 Mar2026-05-31T16:03:11.716Z2025-02-19T01:27:26.612ZS-EPMC89481583510849510.1016/j.ajhg.2022.01.004