Activity
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| Ataxia and cerebellar anomalies - narrow panel v7.31 | HMBS | Sarah Leigh Publications for gene: HMBS were set to 27558376; 34089223 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v7.25 | HMBS |
Sharon Whatley changed review comment from: Relevant metabolic investigation: urine porphobilinogen Although HMBS biallelic pathogenic variants are very rare (8 families worldwide to date) three families (7 individuals) have been shown to have cerebellar ataxia. PMID: 1577472 Llewellyn reported two siblings with HMBS biallelic pathogenic variants c.499C>T, p.(Arg167Trp) and c.500G>A, p.(Arg167Gln). At the age of 18 months one patient had ataxia with intention tremor and dysarthria secondary to partial agenesis of the cerebella vermis bilateral cataracts and right optic nerve hypoplasia. Biochemical studies showed excessive excretion of PBG with normal faecal porphyrin and very low erythrocyte PBG deaminase activity. At 3 years of age, she was admitted to hospital following febrile convulsions. When assessed one year later, she had had no further convulsions or symptoms of acute porphyria. She died at 8 years of age. PMID: 15828996 Sheppard reported on the sibling of the above patient. He had no cataracts or other abnormalities with a normal cerebral ultrasound at birth. Urine PBG was raised and erythrocyte PBG-deaminase activity was very low. Developmental progress was normal up to 18 months old. At 10 years of age clinical signs included severe ataxia, peripheral neuropathy and dysarthria. Urinary porphyrins were continuously elevated in this patient. PMID: 27558376 Kevelam reports 3 siblings with cerebellar ataxia see previous review. PMID: 34089223 Stutterd reported two siblings and an unrelated patient with ataxia see previous review. Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the HMBS gene, due to its low clinical penetrance.; to: Relevant metabolic investigation: urine porphobilinogen Although HMBS biallelic pathogenic variants are very rare (8 families worldwide to date) three families (7 individuals) have been shown to have cerebellar ataxia. PMID: 1577472 Llewellyn reported two siblings with HMBS biallelic pathogenic variants c.499C>T, p.(Arg167Trp) and c.500G>A, p.(Arg167Gln). At the age of 18 months one patient had ataxia with intention tremor and dysarthria secondary to partial agenesis of the cerebella vermis, bilateral cataracts and right optic nerve hypoplasia. Biochemical studies showed excessive excretion of PBG with normal faecal porphyrin and very low erythrocyte PBG deaminase activity. At 3 years of age, she was admitted to hospital following febrile convulsions. When assessed one year later, she had had no further convulsions or symptoms of acute porphyria. She died at 8 years of age. PMID: 15828996 Sheppard reported on the sibling of the above patient. He had no cataracts or other abnormalities with a normal cerebral ultrasound at birth. Urine PBG was raised and erythrocyte PBG-deaminase activity was very low. Developmental progress was normal up to 18 months old. At 10 years of age clinical signs included severe ataxia, peripheral neuropathy and dysarthria. Urinary porphyrins were continuously elevated in this patient. PMID: 27558376 Kevelam reports 3 siblings with cerebellar ataxia see previous review. PMID: 34089223 Stutterd reported two siblings and an unrelated patient with ataxia see previous review. Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the HMBS gene, due to its low clinical penetrance. |
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| Ataxia and cerebellar anomalies - narrow panel v7.25 | HMBS | Sharon Whatley reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 1577472, 15828996; Phenotypes: Leukoencephalopathy, HP:0002352, cerebellar ataxia, MONDO:0000437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v6.3 | HMBS | Sarah Leigh Tag Q1_24_promote_green was removed from gene: HMBS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v6.3 | HMBS | Sarah Leigh reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v6.2 | HMBS |
Sarah Leigh Source NHS GMS was added to HMBS. Source Expert Review Green was added to HMBS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Ataxia and cerebellar anomalies - narrow panel v4.54 | HMBS | Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are three unrelated families reported with ataxia. Hence, this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: There are three unrelated families reported with ataxia. Hence, this gene can be promoted to green rating in the next GMS review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.54 | HMBS | Achchuthan Shanmugasundram Classified gene: HMBS as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.54 | HMBS | Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated families reported with ataxia. Hence, this gene can be promoted to green rating in the next GMS review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.54 | HMBS | Achchuthan Shanmugasundram Gene: hmbs has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.53 | HMBS | Achchuthan Shanmugasundram Phenotypes for gene: HMBS were changed from Leukoencephalopathy, HP:0002352; hereditary spastic paraplegia, MONDO:0019064 to Leukoencephalopathy, HP:0002352; cerebellar ataxia, MONDO:0000437 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.52 | HMBS | Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: HMBS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.52 | HMBS | Achchuthan Shanmugasundram edited their review of gene: HMBS: Changed phenotypes to: Leukoencephalopathy, HP:0002352, cerebellar ataxia, MONDO:0000437 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.52 | HMBS |
Achchuthan Shanmugasundram gene: HMBS was added gene: HMBS was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature Mode of inheritance for gene: HMBS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HMBS were set to 27558376; 34089223 Phenotypes for gene: HMBS were set to Leukoencephalopathy, HP:0002352; hereditary spastic paraplegia, MONDO:0019064 Review for gene: HMBS was set to GREEN Added comment: PMID:27558376 reported three siblings with compound heterozygous missense HMBS variants (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln) and a disease characterised by childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. They had a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons, and cerebellar atrophy was present in advanced disease stages. PMID:34089223 reported two patients from a family with homozygous variant (c.251C>A/ p.Ala84Asp) and another patient from a different family with the same compound heterozygous variants as the siblings reported in PMID:27558376 (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln). All patients presented with slowly progressive spasticity, ataxia, peripheral neuropathy, with or without mild cognitive impairment, and/or ocular disease with onset in childhood or adolescence. Their brain MRIs show mainly confluent signal abnormalities in the periventricular and deep white matter and bilateral thalami. However, the onset of the disease was during childhood in individuals with the homozygous variant (7 years and late childhood), while the onset was at 22 years of age in the third individual with compound heterozygous variants. Monoallelic variants in HMBS gene have been associated with acute intermittent porphyria (MIM #176000) in OMIM, but biallelic variants have not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype. Sources: Literature |
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