TECPR2 mutations cause a new subtype of familial dysautonomia like hereditary sensory autonomic neuropathy with intellectual disability. (January 2016)

• Record Type: Journal Article
• Authors: Heimer, Gali; Oz-Levi, Danit; Eyal, Eran; Edvardson, Shimon; Nissenkorn, Andreea; Ruzzo, Elizabeth K.; Szeinberg, Amir; Maayan, Channa; Mai-Zahav, Meir; Efrati, Ori; Pras, Elon; Reznik-Wolf, Haike; Lancet, Doron; Goldstein, David B.; Anikster, Yair; Shalev, Stavit A.; Elpeleg, Orly; Ben Zeev, Bruria
• Is Part Of: European journal of paediatric neurology. Volume 20:Number 1(2016:Jan.)
• Page Start: 69
• Page End: 79
• Publication Date: 2016-01
• Subjects: TECPR2 -- Autophagy -- HSAN III -- IKBKAP -- Hereditary spastic paraparesis -- Jewish Ashkenazi; Pediatric neurology -- Periodicals; Nervous System Diseases -- Periodicals; Child -- Periodicals; Infant -- Periodicals; Neurologie pédiatrique -- Périodiques; Pediatric neurology; Electronic journals; Periodicals; Electronic journals; 618.928
• DOI: 10.1016/j.ejpn.2015.10.003
• Languages: English
• ISSNs: 1090-3798

Abstract

Abstract: Background: TECPR2 was first described as a disease causing gene when the c.3416delT frameshift mutation was found in five Jewish Bukharian patients with similar features. It was suggested to constitute a new subtype of complex hereditary spastic paraparesis (SPG49). Results: We report here 3 additional patients from unrelated non-Bukharian families, harboring two novel mutations (c.1319delT, c.C566T) in this gene. Accumulating clinical data clarifies that in addition to intellectual disability and evolving spasticity the main disabling feature of this unique disorder is autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events. Conclusion: We suggest that the disease should therefore be classified as a new subtype of hereditary sensory-autonomic neuropathy. The discovery of additional mutations in non-Bukharian patients implies that this disease might be more common than previously appreciated and should therefore be considered in undiagnosed cases of intellectual disability with autonomic features and respiratory symptoms regardless of demographic origin. Highlights: We report 3 non-Bukharian patients, with 2 novel mutations in the TECPR2 gene. Their main disabling features are autonomic neuropathy, respiratory disease and ID. TECPR2 disorder should be classified as a subtype of sensory autonomic neuropathy. It is not limited to Bukharian origin and might be more common than formerly assumed. It should be considered in Riley Day like patients with ID and no IKBKAP mutations.