NOTCH2NLC CGG Repeats Are Not Expanded and Skin Biopsy Was Negative in an Infantile Patient With Neuronal Intranuclear Inclusion Disease. Issue 10 (22nd August 2020)

• Record Type: Journal Article
• Authors: Jedlickova, Ivana; Pristoupilova, Anna; Hulkova, Helena; Vrbacka, Alena; Stranecky, Viktor; Hruba, Eva; Jesina, Pavel; Honzik, Tomas; Hrdlicka, Ivan; Fremuth, Jiri; Pivovarcikova, Kristyna; Bitar, Ibrahim; Matej, Radoslav; Kmoch, Stanislav; Sikora, Jakub
• Is Part Of: Journal of neuropathology and experimental neurology. Volume 79:Issue 10(2020)
• Page Start: 1065
• Page End: 1071
• Publication Date: 2020-08-22
• Subjects: Cerebellum -- Infantile neuronal intranuclear inclusion disease -- Neuropathology -- NOTCH2NLC -- Trinucleotide repeat expansions; Neurology -- Diseases -- Periodicals; Neurology -- Diseases -- Physiopathology -- Periodicals; 616.8047
• DOI: 10.1093/jnen/nlaa070
• Languages: English
• ISSNs: 0022-3069

Abstract

Abstract: Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disorder categorized into 3 phenotypic variants: infantile, juvenile, and adult. Four recent reports have linked NIID to CGG expansions in the NOTCH2NLC gene in adult NIID (aNIID) and several juvenile patients. Infantile NIID (iNIID) is an extremely rare neuropediatric condition. We present a 7-year-old male patient with severe progressive neurodegenerative disease that included cerebellar symptoms with cerebellar atrophy on brain MRI, psychomotor developmental regression, pseudobulbar syndrome, and polyneuropathy. The diagnosis of iNIID was established through a postmortem neuropathology work-up. We performed long-read sequencing of the critical NOTCH2NLC repeat motif and found no expansion in the patient. We also re-evaluated an antemortem skin biopsy that was collected when the patient was 2 years and 8 months old and did not identify the intranuclear inclusions. In our report, we highlight that the 2 methods (skin biopsy and CGG expansion testing in NOTCH2NLC ) used to identify aNIID patients may provide negative results in iNIID patients.