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| Prepair 1000+ v1.1994 | MICU1 | Zornitza Stark Phenotypes for gene: MICU1 were changed from Myopathy with extrapyramidal signs, 615673 (3) to Myopathy with extrapyramidal signs, MIM# 615673 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1822 | MICU1 | Melanie Marty reviewed gene: MICU1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24336167, 29721912, 32395406; Phenotypes: Myopathy with extrapyramidal signs, MIM# 615673; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1568 | DLAT |
Andrew Coventry gene: DLAT was added gene: DLAT was added to Prepair 1000+. Sources: Literature Mode of inheritance for gene: DLAT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DLAT were set to 34138529; 16049940; 20022530; 29093066 Phenotypes for gene: DLAT were set to Leigh syndrome MONDO:0009723; Pyruvate dehydrogenase E2 deficiency MIM#245348 Review for gene: DLAT was set to GREEN Added comment: Clinical presentation is in infancy. Pyruvate dehydrogenase E2 deficiency is a mitochondrial disorder, mostly affects the brain and leads to decreased ATP production and energy deficit. Can manifest as a syndrome of neurologic signs (congenital microcephaly, hypotonia, epilepsy, and/or ataxia), brain impacts (dysgenesis of the corpus callosum, Leigh syndrome) and metabolic abnormalities (increased plasma pyruvate, lactic acidemia, and/or metabolic acidosis). Biochemical function, expression data, and model systems available. 1-4% of total PDE2D cases are due to variants in DLAT - associated with phenotype w/survival into childhood/adulthood, milder than other genes involved with condition. PMID: 16049940 - 2 unrelated patients with Episodic dystonia. Hypotonia and ataxia, being less prominent. Neuroradiological evidence of discrete lesions restricted to the globus pallidus, Male patient 1 - dystonic movements of the facial muscles and of his hands and feet.Developmental delay (12 words at age 4). Treatment has improved condition. Male patient 2 - presented at 11 months of age with episodic dystonia (up to 3hrs duration). 8 years of age, developmental delay, cannot walk. PMID: 29093066 - 2 siblings (both homozygous for c.470T>G; p.Val157Gly). Male sibling reported with intellectual disability and exercise-induced gait abnormalities. IQ of 44 at 8 years of age. Female sibling noted to have global delays with intellectual disability. PMID: 20022530 - two sisters with early onset episodic dystonia and pyruvate dehydrogenase deficiency. At least 6 cases, in 4 unrelated families as described in publications above. While reportedly milder than other presentations, appears severe presentation in absence of treatment. Other genes currently included: PDHA1, PDHB, PDP1. Sources: Literature |
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| Prepair 1000+ v1.992 | PC |
Ee Ming Wong changed review comment from: - Well-established gene disease association - Age of onset: neonatal to early childhood - Severity: variable severity - three subtypes 1. Type A (infantile form aka North American form): characterized by infantile onset of metabolic and lactic acidosis, delayed motor development, intellectual disability, poor linear growth and/or weight gain, and neurologic findings. Brain anomalies can be noted. Most affected children die in infancy or early childhood. 2. Type B (severe neonatal form aka French form): characterized by neonatal or infantile onset of hypothermia, respiratory distress/failure, vomiting, severe lactic acidosis, hyperammonemia, and often hypoglycemia. Neurologic findings include brain abnormalities, lethargy, hypotonia, and pyramidal and extrapyramidal signs. Death typically occurs by age eight months. 3. Type C (intermittent/attenuated form aka Benign form): characterized by relatively normal or mildly delayed neurologic development, motor and/or gait abnormalities, (rarely) seizures, episodic movement disorders, and metabolic acidosis. Life span is unknown but survival into adulthood has been reported.; to: - Well-established gene disease association - Age of onset: neonatal to early childhood - Severity: variable severity - three subtypes 1. Type A (infantile form aka North American form): characterized by infantile onset of metabolic and lactic acidosis, delayed motor development, intellectual disability, poor linear growth and/or weight gain, and neurologic findings. Brain anomalies can be noted. Most affected children die in infancy or early childhood. 2. Type B (severe neonatal form aka French form): characterized by neonatal or infantile onset of hypothermia, respiratory distress/failure, vomiting, severe lactic acidosis, hyperammonemia, and often hypoglycemia. Neurologic findings include brain abnormalities, lethargy, hypotonia, and pyramidal and extrapyramidal signs. Death typically occurs by age eight months. 3. Type C (intermittent/attenuated form aka Benign form): characterized by relatively normal or mildly delayed neurologic development, motor and/or gait abnormalities, (rarely) seizures, episodic movement disorders, and metabolic acidosis. Life span is unknown but survival into adulthood has been reported. |
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| Prepair 1000+ v1.627 | GNS | Lilian Downie Marked gene: GNS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.627 | GNS | Lilian Downie Gene: gns has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.627 | GNS | Lilian Downie Publications for gene: GNS were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.553 | GNS | Ee Ming Wong reviewed gene: GNS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31536183; Phenotypes: Mucopolysaccharidosis type IIID, MIM# 252940, Sanfilippo syndrome type D, MONDO:0009658; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.525 | SPG11 |
Lucy Spencer changed review comment from: OMIM: Charcot-Marie-Tooth disease type 2X (CMT2X) is an autosomal recessive, slowly progressive, axonal peripheral sensorimotor neuropathy characterized by lower limb muscle weakness and atrophy associated with distal sensory impairment and gait difficulties. Some patients also have involvement of the upper limbs. Onset usually occurs in the first 2 decades of life, although later onset can also occur (summary by Montecchiani et al., 2016). Mean age of onset 11.4 years. Hereditary spastic paraplegia (SPG or HSP) is characterized by progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. SPG11 is a form of complicated SPG, in that it has neurologic features in addition to spasticity. ClinGen lumps all 3 conditions under spastic paraplegia 11 Autosomal recessive juvenile amyotrophic lateral sclerosis-5 (ALS5) is a neurodegenerative disorder characterized by onset of upper and lower motor neuron signs before age 25. Affected individuals have progressive spasticity of limb and facial muscles associated with distal amyotrophy. The disorder is slowly progressive, with cases of prolonged survival of more than 3 decades (summary by Orlacchio et al., 2010).; to: OMIM: Charcot-Marie-Tooth disease type 2X (CMT2X) is an autosomal recessive, slowly progressive, axonal peripheral sensorimotor neuropathy characterized by lower limb muscle weakness and atrophy associated with distal sensory impairment and gait difficulties. Some patients also have involvement of the upper limbs. Onset usually occurs in the first 2 decades of life, although later onset can also occur (summary by Montecchiani et al., 2016). Mean age of onset 11.4 years. Hereditary spastic paraplegia (SPG or HSP) is characterized by progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. SPG11 is a form of complicated SPG, in that it has neurologic features in addition to spasticity. Autosomal recessive juvenile amyotrophic lateral sclerosis-5 (ALS5) is a neurodegenerative disorder characterized by onset of upper and lower motor neuron signs before age 25. Affected individuals have progressive spasticity of limb and facial muscles associated with distal amyotrophy. The disorder is slowly progressive, with cases of prolonged survival of more than 3 decades (summary by Orlacchio et al., 2010). These 3 conditions represent a spectrum of disease and ClinGen lumps all 3 conditions under hereditary spastic paraplegia 11 MONDO:0011445 |
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| Prepair 1000+ v1.486 | SPG11 |
Lucy Spencer changed review comment from: OMIM: Charcot-Marie-Tooth disease type 2X (CMT2X) is an autosomal recessive, slowly progressive, axonal peripheral sensorimotor neuropathy characterized by lower limb muscle weakness and atrophy associated with distal sensory impairment and gait difficulties. Some patients also have involvement of the upper limbs. Onset usually occurs in the first 2 decades of life, although later onset can also occur (summary by Montecchiani et al., 2016). Mean age of onset 11.4 years. Hereditary spastic paraplegia (SPG or HSP) is characterized by progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. SPG11 is a form of complicated SPG, in that it has neurologic features in addition to spasticity. Autosomal recessive juvenile amyotrophic lateral sclerosis-5 (ALS5) is a neurodegenerative disorder characterized by onset of upper and lower motor neuron signs before age 25. Affected individuals have progressive spasticity of limb and facial muscles associated with distal amyotrophy. The disorder is slowly progressive, with cases of prolonged survival of more than 3 decades (summary by Orlacchio et al., 2010).; to: OMIM: Charcot-Marie-Tooth disease type 2X (CMT2X) is an autosomal recessive, slowly progressive, axonal peripheral sensorimotor neuropathy characterized by lower limb muscle weakness and atrophy associated with distal sensory impairment and gait difficulties. Some patients also have involvement of the upper limbs. Onset usually occurs in the first 2 decades of life, although later onset can also occur (summary by Montecchiani et al., 2016). Mean age of onset 11.4 years. Hereditary spastic paraplegia (SPG or HSP) is characterized by progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. SPG11 is a form of complicated SPG, in that it has neurologic features in addition to spasticity. ClinGen lumps all 3 conditions under spastic paraplegia 11 Autosomal recessive juvenile amyotrophic lateral sclerosis-5 (ALS5) is a neurodegenerative disorder characterized by onset of upper and lower motor neuron signs before age 25. Affected individuals have progressive spasticity of limb and facial muscles associated with distal amyotrophy. The disorder is slowly progressive, with cases of prolonged survival of more than 3 decades (summary by Orlacchio et al., 2010). |
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| Prepair 1000+ v1.5 | ADPRHL2 |
Zornitza Stark changed review comment from: Fourteen unrelated families reported with stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS), an autosomal recessive neurodegenerative disorder with onset in the first years of life following normal early development. The disorder is characterised by cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some individuals develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy. New HGNC approved name is ADPRS.; to: Fourteen unrelated families reported with stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS), an autosomal recessive neurodegenerative disorder with onset in the first years of life following normal early development. The disorder is characterised by cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some individuals develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy. New HGNC approved name is ADPRS. To be upgraded to GREEN in next version of panel. |
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| Prepair 1000+ v1.3 | GNS | Seb Lunke Added phenotypes Mucopolysaccharidosis type IIID, 252940 (3) for gene: GNS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | MICU1 |
Zornitza Stark gene: MICU1 was added gene: MICU1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: MICU1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MICU1 were set to Myopathy with extrapyramidal signs, 615673 (3) |
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| Prepair 1000+ v0.0 | GNS |
Zornitza Stark gene: GNS was added gene: GNS was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: GNS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GNS were set to Mucopolysaccharidosis type IIID, 252940 (3) |
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