First report of novel mutation (c.790del) on SQSTM1 gene on a family with childhood onset of progressive cerebellar ataxia with vertical gaze palsy

Abstract

SQSTM1 gene encodes a protein called p62 that acts as an autophagy receptor in the degradation of protein molecules. A homozygous deletion variant that changes the frame shift in the SQSTM1 gene named c.790 Del A .T was detected in case childhood onset and progressive neurodegeneration with ataxia, and gaze palsy.

Cognitive Impairment, Ataxia, Dystonia, and Gaze Palsy Due to a Novel Variant in SQSTM1: New Lessons

“…3,4 Dopamine has been assumed to exert its pain-relieving effects at cortical and spinal levels, 4,5 whereas only cortical effects were described for DBS thus far. 6 The nociceptive flection reflex (NFR) threshold, reflecting spinal nociception, was assessed during medication on (MEDon) by the Paintracker (www.dolosys.com): (1) once with the DBS switched ON (DBS-ON); (2) twice with the device switched OFF (DBS-OFF); and (3) once with the device switched ON again (DBS-ON). Automatic threshold determination lasted 5 minutes (30 stimuli with 10-second interstimulus interval).…”

“…1 Subsequently, further cases were reported (Table S1). [3][4][5][6][7][8][9] Prominent features include cognitive impairment, ataxia, dystonia. and gaze palsy (Table S2).…”

A Novel Variant in SQSTM1 Gene Causing Neurodegeneration with Ataxia, Dystonia, and Gaze Palsy in a Peruvian Family

“…There are at least 30 cases with NADGP reported worldwide. The classical phenotype includes progressive ataxia, dystonia, gaze palsy and learning difficulties, [1][2][3][4] however, clinical symptoms can vary even within the same family.…”

“…7 Three affected siblings experienced early-onset ataxia with ophthalmoparesis, cognitive impairment, and hyperkinetic movements, consistent with previous reports of individuals with NADGP. [1][2][3][4] The combination of vertical gaze impairment, dystonia "facial grimacing" and ataxia have been reported in few disorders like Niemann-Pick type C and GM1-gangliosidosis type 3. 8,9 Two siblings (II-1, II-2) also experienced dysautonomic symptoms, considered less frequent symptoms of NADGP.…”