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IEMbase 0312: MFSD8-related CLN7 Turkish variant

Scope

Field Value
IEMbase ID 312
Nosology 20.4.06.01
Gene MFSD8
External IDs OMIM:610951; ORPHA:228366
Generated mapping MAPPED; Neuronal_Ceroid_Lipofuscinosis_7.yaml
Candidate DisMech targets Neuronal_Ceroid_Lipofuscinosis_7.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents MFSD8-related CLN7/variant late-infantile NCL with behavioral disorder, cerebellar atrophy, cerebral atrophy, movement disorder, muscular atrophy, seizures, spinal muscular atrophy, and vision loss or optic atrophy. Additional clinical rows include ataxia, cerebellar white matter abnormalities, developmental regression, dystonia, abnormal EEG, abnormal ERG, myoclonic epilepsy, myoclonus, neurodegenerative disease, optic atrophy, pigmentary retinopathy, retinal dystrophy, myoclonic and tonic-clonic seizures, abnormal somatosensory evoked potentials, spasticity, abnormal or delayed speech, and abnormal VEP.

No biochemical rows are present. The treatment row is intrathecal Milasen, classified as gene-based in the cached record.

DisMech phenotype coverage

Neuronal_Ceroid_Lipofuscinosis_7.yaml is the correct local target. It models MFSD8 biallelic pathogenic variants, MFSD8 lysosomal membrane protein dysfunction, lysosomal autofluorescent storage material, impaired autophagy, abnormal neuronal mitochondria accumulation, elevated mitochondrial reactive oxygen species, aberrant PFKFB3 activation, and progressive neurodegeneration.

Phenotype coverage includes seizures, psychomotor deterioration, cognitive decline, motor decline, behavioral impairment, myoclonus, retinal degeneration with visual impairment, and visual impairment. Biochemical/model readouts include mitochondrial reactive oxygen species and PFKFB3 activation. Treatments include AAV9/MFSD8 gene therapy, Milasen patient-customized splice-modulating ASO, and PFKFB3 inhibitor AZ67.

Concordance and completeness

Judgement: correct high-confidence mapping to Neuronal_Ceroid_Lipofuscinosis_7.yaml.

Concordance is high for MFSD8 identity, CLN7 scope, seizures, developmental or psychomotor deterioration, behavioral impairment, myoclonus, motor decline, retinal degeneration, visual impairment, and Milasen as a patient-customized gene-based/ASO therapy. DisMech is richer for MFSD8 mechanism, model-system biomarkers, AAV9/MFSD8, and PFKFB3-directed experimental treatment.

IEMbase adds granular prompts for ataxia, dystonia, spasticity, cerebral and cerebellar atrophy, cerebellar white matter abnormality, optic atrophy, pigmentary retinopathy, EEG/ERG/VEP/SSEP abnormalities, abnormal speech, muscular atrophy, and spinal muscular atrophy. Some of these are compatible with the local phenotype but not yet represented as discrete rows.

Curation actions

  • Keep the generated NCL7 mapping.
  • Consider adding source-backed MRI, optic-atrophy, pigmentary-retinopathy, EEG/ERG/VEP/SSEP, speech, ataxia, dystonia, and spasticity detail.
  • Preserve Milasen as a patient-customized splice-modulating ASO rather than a generic gene therapy if future treatment terms are refined.
  • Review muscular atrophy and spinal muscular atrophy rows before import.