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Leukodystrophy v0.347 Bryony Thompson Copied gene GAN from panel Leukodystrophy - adult onset
Leukodystrophy v0.347 GAN Bryony Thompson gene: GAN was added
gene: GAN was added to Leukodystrophy - paediatric. Sources: Expert Review Red,Royal Melbourne Hospital
Mode of inheritance for gene: GAN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GAN were set to Giant axonal neuropathy-1, MIM#256850
Leukodystrophy v0.309 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID 38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autism and ID GCEP.
Sources: Literature
Leukodystrophy v0.204 HPDL Zornitza Stark gene: HPDL was added
gene: HPDL was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPDL were set to 32707086
Phenotypes for gene: HPDL were set to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Progressive neurological disorder; Leigh-like syndrome
Review for gene: HPDL was set to GREEN
Added comment: Biallelic variants reported in 13 families with a neurodegenerative disease ranging from neonatal encephalopathy to adolescent-onset spastic paraplegia. Extensive MRI abnormalities described, primarily affecting white matter (white matter atrophy and deficient myelination), basal ganglia, thalamus and brainstem.
Sources: Literature
Leukodystrophy v0.161 RNASEH2B Zornitza Stark gene: RNASEH2B was added
gene: RNASEH2B was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: RNASEH2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2B were set to 16845400
Phenotypes for gene: RNASEH2B were set to Aicardi-Goutieres syndrome 2, MIM# 610181
Review for gene: RNASEH2B was set to GREEN
Added comment: Leukodystrophy is common in AGS in general, though basal ganglia calcification seems to predominate here.
Sources: Expert list
Leukodystrophy v0.126 CNP Kristin Rigbye gene: CNP was added
gene: CNP was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: CNP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNP were set to 32128616; 12590258
Phenotypes for gene: CNP were set to Hypomyelinating leukodystrophy
Review for gene: CNP was set to AMBER
Added comment: Single consanguineous family described with homozygous missense in affected child (additional two affected deceased offspring unavailable for testing; healthy carrier parents and sibling).
Loss of protein by Western blot and defect in F-actin structure and organization observed in patient fibroblasts.
Deficiency of CNP in mouse has previously been shown to cause a lethal white matter neurodegenerative phenotype (PMID: 12590258), similar to the phenotype observed in this family.
Sources: Literature
Leukodystrophy v0.109 GLB1 Zornitza Stark gene: GLB1 was added
gene: GLB1 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: GLB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLB1 were set to 25691190
Phenotypes for gene: GLB1 were set to GM1-gangliosidosis, type I, MIM# 230500; GM1-gangliosidosis, type II, MIM# 230600
Review for gene: GLB1 was set to GREEN
Added comment: Sources: Expert list