Activity

Filter

Cancel
Date Panel Item Activity
11 actions
Hereditary neuropathy or pain disorder v8.28 APOPT1 Achchuthan Shanmugasundram Classified gene: APOPT1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v8.28 APOPT1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated patients with biallelic APOPT1 variants and presenting with neuropathy. Hence, this gene can be promoted to green rating on this panel in the next GMS update.
Hereditary neuropathy or pain disorder v8.28 APOPT1 Achchuthan Shanmugasundram Gene: apopt1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v8.27 APOPT1 Achchuthan Shanmugasundram commented on gene: APOPT1: The 'new-gene-name' tag has been added as the official HGNC gene symbol for APOPT1 is COA8.
Hereditary neuropathy or pain disorder v8.27 APOPT1 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: APOPT1.
Hereditary neuropathy or pain disorder v8.27 APOPT1 Achchuthan Shanmugasundram Phenotypes for gene: APOPT1 were changed from 25175347; 38098475Encephalopathic episodes; loss of developmental milestones; seizures; spasticity; cavitating leukodystrophy to Mitochondrial complex IV deficiency, nuclear type 17, OMIM:619061; mitochondrial complex IV deficiency, nuclear type 17, MONDO:0033652; peripheral neuropathy, MONDO:0005244
Hereditary neuropathy or pain disorder v8.26 APOPT1 Achchuthan Shanmugasundram Tag Q3_26_NHS_review tag was added to gene: APOPT1.
Tag Q3_26_promote_green tag was added to gene: APOPT1.
Hereditary neuropathy or pain disorder v8.26 APOPT1 Achchuthan Shanmugasundram changed review comment from: PMID:25175347 (2014) reported a total of six patients from five unrelated families identified with biallelic variants in APOPT1 gene. There were six different variants identified from these patients and all but one were homozygous, and one individual had compound heterozygous variants. The clinical features of all six patients varied widely from acute neurometabolic decompensation in late infancy to subtle neurological signs, which appeared in adolescence; all presented a chronic, long-surviving clinical course. Peripheral neuropathy was reported in two patients; to: PMID:25175347 (2014) reported a total of six patients from five unrelated families identified with biallelic variants in APOPT1 gene. There were six different variants identified from these patients and all but one were homozygous, and one individual had compound heterozygous variants. Across the six individuals with APOPT1 mutations, all show infantile or childhood‑onset mitochondrial disease with profound COX deficiency, a characteristic cavitating leukodystrophy on MRI predominantly affecting posterior cerebral white matter and corpus callosum, and evidence of peripheral neuropathy. Clinically, they range from acute neurometabolic decompensation with spastic tetraparesis, seizures and cognitive impairment to much milder phenotypes with preserved cognition, but all have a chronic, long‑surviving course with stabilization or partial recovery of motor function despite persistent structural white matter changes. Sensorimotor polyneuropathy was reported in three of the six patients.

PMID:38098475 (2023) reported two female siblings from an Italian family with mitochondrial myopathy. Patient 1 presented with generalised epilepsy and retinitis pigmentosa at 10 years of age. She had cramps and myalgia after exercise and bilateral hearing loss since early adulthood. Last neurological examination (52 years of age) showed bilateral ptosis, muscle weakness, peripheral neuropathy, mild dysarthria, dysphonia and cognitive impairment. Muscle biopsy had shown the presence of ragged-red fibers. Patient 2 presented with fatigability, myalgia, and hearing loss. Neurological examination showed ptosis and muscle weakness. Muscle biopsy displayed a diffuse reduction of COX activity staining and ragged-red fibers. Both sisters presented secondary amenorrhea. A novel homozygous variant in COA8 (APOPT1) was identified via whole-exome sequencing in the probands (c.170_173dupGACC, p.Pro59fs).

This gene has been associated with relevant phenotype in OMIM (MIM #619061, last accessed 28 July 2026), Gene2Phenotype (with 'definitive' rating on the DD and Eye panels) and in ClinGen (associated with 'definitive' rating for mitochondrial disease (MONDO:0044970) by Mitochondrial Diseases GCEP - https://search.clinicalgenome.org/CCID:004493).
Hereditary neuropathy or pain disorder v8.24 APOPT1 Achchuthan Shanmugasundram commented on gene: APOPT1: PMID:25175347 (2014) reported a total of six patients from five unrelated families identified with biallelic variants in APOPT1 gene. There were six different variants identified from these patients and all but one were homozygous, and one individual had compound heterozygous variants. The clinical features of all six patients varied widely from acute neurometabolic decompensation in late infancy to subtle neurological signs, which appeared in adolescence; all presented a chronic, long-surviving clinical course. Peripheral neuropathy was reported in two patients
Hereditary neuropathy or pain disorder v8.24 APOPT1 Achchuthan Shanmugasundram reviewed gene: APOPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25175347, 38098475; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 17, OMIM:619061, mitochondrial complex IV deficiency, nuclear type 17, MONDO:0033652, peripheral neuropathy, MONDO:0005244; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v7.45 APOPT1 Alexander Rossor gene: APOPT1 was added
gene: APOPT1 was added to Hereditary neuropathy or pain disorder. Sources: Expert list
Mode of inheritance for gene: APOPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APOPT1 were set to 25175347; 38098475
Phenotypes for gene: APOPT1 were set to 25175347; 38098475Encephalopathic episodes; loss of developmental milestones; seizures; spasticity; cavitating leukodystrophy
Penetrance for gene: APOPT1 were set to Complete
Review for gene: APOPT1 was set to GREEN
Added comment: Sources: Expert list