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Neurodegenerative disorders, adult onset v9.27 LAMB1 Ida Ertmanska Phenotypes for gene: LAMB1 were changed from Lissencephaly 5, OMIM:615191; cobblestone lissencephaly without muscular or ocular involvement, MONDO:0014077 to Leukoencephalopathy without lacunae, adult-onset, OMIM:621424; leukoencephalopathy without lacunae, adult-onset, MONDO:0980752; Leukoencephalopathy with variable cortical brain malformations and/or hydrocephalus, OMIM:615191
Neurodegenerative disorders, adult onset v9.26 LAMB1 Ida Ertmanska Publications for gene: LAMB1 were set to 32548278; 34606115; 23472759; 25925986; 29888467
Neurodegenerative disorders, adult onset v9.25 LAMB1 Ida Ertmanska Tag Q4_26_expert_review tag was added to gene: LAMB1.
Tag Q4_26_MOI tag was added to gene: LAMB1.
Neurodegenerative disorders, adult onset v9.25 LAMB1 Ida Ertmanska commented on gene: LAMB1: Comment on mode of inheritance: There are multiple patients reported with heterozygous frameshift LAMB1 variants and an adult-onset cerebral small vessel disease with leukoencephalopathy. There is only one individual reported to date with a biallelic missense variant and an adult-onset neurodegenerative disorder (PMID: 32548278). Hence, the mode of inheritance of this gene should be changed to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted', with expert review to ensure GMS agreement on this MOI 'demotion'.
Neurodegenerative disorders, adult onset v9.25 LAMB1 Ida Ertmanska edited their review of gene: LAMB1: Changed publications to: 32548278, 34606115, 37063705, 39082428
Neurodegenerative disorders, adult onset v9.25 LAMB1 Ida Ertmanska changed review comment from: PMID: 32548278 Yasuda et al., 2020
Report of a 37-year-old Japanese woman with headache, memory loss, mild flexion of retinal vessels, and gait disturbance. She was born to consanguineous parents. Her symptoms started at 22 yrs with a migraine. Brain MRI showed a cerebral white matter lesion at age 30 years. Wechsler Adult Intelligence Scale–Third Edition indicated a full-scale IQ of 69 - borderline ID. Seq method: targeted exome seq of 115 genes. She was found to be homozygous for LAMB1: c.1378T>C, p.Cys460Arg variant. Parents confirmed het. There is only 1 het individual reported in gnomAD v4.1.2 with this variant. Authors pose that "the effect of missense mutations on the phenotype may be milder compared with that of frameshift mutations."
Functional support: PMID: 40237576 Yasuda et al., 2025 - Drosophila melanogaster model. Study found that the LAMB1 fly ortholog LanB1 gene is expressed on the surface of adult fly brains in a subset of glia cells. While human LAMB1 was not able to function in flies, in vivo overexpression and rescue experiments using analogous variants in fly LanB1 suggested that the frameshift variants behave as strong LoF alleles whereas a missense variant functions as a milder LoF allele.

LAMB1 is associated with AD Leukoencephalopathy without lacunae, adult-onset, OMIM:621424 & AR Leukoencephalopathy with variable cortical brain malformations and/or hydrocephalus, OMIM:615191 (OMIM accessed 9th Oct 2026).; to: PMID: 32548278 Yasuda et al., 2020 - BIALLELIC ADULT CASE
Report of a 37-year-old Japanese woman with headache, memory loss, mild flexion of retinal vessels, and gait disturbance. She was born to consanguineous parents. Her symptoms started at 22 yrs with a migraine. Brain MRI showed a cerebral white matter lesion at age 30 years. Wechsler Adult Intelligence Scale–Third Edition indicated a full-scale IQ of 69 - borderline ID. Seq method: targeted exome seq of 115 genes. She was found to be homozygous for LAMB1: c.1378T>C, p.Cys460Arg variant. Parents confirmed het. There is only 1 het individual reported in gnomAD v4.1.2 with this variant. Authors pose that "the effect of missense mutations on the phenotype may be milder compared with that of frameshift mutations."
Functional support: PMID: 40237576 Yasuda et al., 2025 - Drosophila melanogaster model. Study found that the LAMB1 fly ortholog LanB1 gene is expressed on the surface of adult fly brains in a subset of glia cells. While human LAMB1 was not able to function in flies, in vivo overexpression and rescue experiments using analogous variants in fly LanB1 suggested that the frameshift variants behave as strong LoF alleles whereas a missense variant functions as a milder LoF allele.

MONOALLELIC ADULT CASES:
PMID: 34606115 Aloui et al., 2021 - exome data of 258 cerebral small vessel disease patients. 4 patients had het frameshift variants in LAMB1 residues 1721-1750 - predicted to escape NMD (plus P5 with a het splice variant but not much detail provided). Age at first symptom was 20-67 yrs for patients 1-4. Common phenotype was hippocampal memory defect and leukoencephalopathy.

PMID: 37063705 Morel et al., 2023 - report of 6 patients from 2 unrelated families with het end-truncating LAMB1 variations escaping NMD. Method: targeted seq of 8 cerebral small vessel disease genes. Patients were 30-80 yo at examination. The 4 patients older than 50 years presented with an amnestic syndrome of the hippocampal type (ASHT) with mild executive dysfunction and diffuse leukoencephalopathy. Significant cognitive complaints were also present in the 2 younger patients.

PMID: 39082428 Cho et al., 2024 - Cohort of 257 suspected Cerebral Small-Vessel Disease cases. P11 had a het LAMB1 variant p.Leu1730Ter. She had memory deficit and migraine with aura when she was recruited. She had transient ischemic attack at the age of 57 years, stroke at the age of 61 years, and passed away at the age of 67 years. Brain MRI taken at the age of 64 years showed extensive confluent white matter hyperintensities, and lacunar infarcts

LAMB1 is associated with AD Leukoencephalopathy without lacunae, adult-onset, OMIM:621424 & AR Leukoencephalopathy with variable cortical brain malformations and/or hydrocephalus, OMIM:615191 (OMIM accessed 9th Oct 2026).
Neurodegenerative disorders, adult onset v9.25 LAMB1 Ida Ertmanska changed review comment from: PMID: 32548278 Yasuda et al., 2020
Report of a 37-year-old Japanese woman with headache, memory loss, mild flexion of retinal vessels, and gait disturbance. She was born to consanguineous parents. Her symptoms started at 22 yrs with a migraine. Brain MRI showed a cerebral white matter lesion at age 30 years. Wechsler Adult Intelligence Scale–Third Edition indicated a full-scale IQ of 69 - borderline ID. Seq method: targeted exome seq of 115 genes. She was found to be homozygous for LAMB1: c.1378T>C, p.Cys460Arg variant. Parents confirmed het. There is only 1 het individual reported in gnomAD v4.1.2 with this variant. Authors pose that "the effect of missense mutations on the phenotype may be milder compared with that of frameshift mutations."

LAMB1 is associated with AD Leukoencephalopathy without lacunae, adult-onset, OMIM:621424 & AR Leukoencephalopathy with variable cortical brain malformations and/or hydrocephalus, OMIM:615191 (OMIM accessed 9th Oct 2026).; to: PMID: 32548278 Yasuda et al., 2020
Report of a 37-year-old Japanese woman with headache, memory loss, mild flexion of retinal vessels, and gait disturbance. She was born to consanguineous parents. Her symptoms started at 22 yrs with a migraine. Brain MRI showed a cerebral white matter lesion at age 30 years. Wechsler Adult Intelligence Scale–Third Edition indicated a full-scale IQ of 69 - borderline ID. Seq method: targeted exome seq of 115 genes. She was found to be homozygous for LAMB1: c.1378T>C, p.Cys460Arg variant. Parents confirmed het. There is only 1 het individual reported in gnomAD v4.1.2 with this variant. Authors pose that "the effect of missense mutations on the phenotype may be milder compared with that of frameshift mutations."
Functional support: PMID: 40237576 Yasuda et al., 2025 - Drosophila melanogaster model. Study found that the LAMB1 fly ortholog LanB1 gene is expressed on the surface of adult fly brains in a subset of glia cells. While human LAMB1 was not able to function in flies, in vivo overexpression and rescue experiments using analogous variants in fly LanB1 suggested that the frameshift variants behave as strong LoF alleles whereas a missense variant functions as a milder LoF allele.

LAMB1 is associated with AD Leukoencephalopathy without lacunae, adult-onset, OMIM:621424 & AR Leukoencephalopathy with variable cortical brain malformations and/or hydrocephalus, OMIM:615191 (OMIM accessed 9th Oct 2026).
Neurodegenerative disorders, adult onset v9.25 LAMB1 Ida Ertmanska reviewed gene: LAMB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32548278; Phenotypes: Leukoencephalopathy without lacunae, adult-onset, OMIM:621424, leukoencephalopathy without lacunae, adult-onset, MONDO:0980752, Leukoencephalopathy with variable cortical brain malformations and/or hydrocephalus, OMIM:615191; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurodegenerative disorders, adult onset v3.49 LAMB1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: LAMB1.
Neurodegenerative disorders, adult onset v3.49 LAMB1 Arina Puzriakova reviewed gene: LAMB1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Neurodegenerative disorders, adult onset v3.48 LAMB1 Arina Puzriakova Source NHS GMS was added to LAMB1.
Source Expert Review Green was added to LAMB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Neurodegenerative disorders, adult onset v3.47 LAMB1 Sarah Leigh Publications for gene: LAMB1 were set to 32548278; 34606115
Neurodegenerative disorders, adult onset v3.46 LAMB1 Sarah Leigh Publications for gene: LAMB1 were set to
Neurodegenerative disorders, adult onset v3.45 LAMB1 Sarah Leigh Phenotypes for gene: LAMB1 were changed from Lissencephaly 5, OMIM:615191 to Lissencephaly 5, OMIM:615191; cobblestone lissencephaly without muscular or ocular involvement, MONDO:0014077
Neurodegenerative disorders, adult onset v3.36 LAMB1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: LAMB1.
Neurodegenerative disorders, adult onset v3.32 LAMB1 Achchuthan Shanmugasundram Phenotypes for gene: LAMB1 were changed from to Lissencephaly 5, OMIM:615191
Neurodegenerative disorders, adult onset v3.31 LAMB1 Achchuthan Shanmugasundram Mode of inheritance for gene: LAMB1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Neurodegenerative disorders, adult onset v3.30 LAMB1 Achchuthan Shanmugasundram Mode of inheritance for gene: LAMB1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Neurodegenerative disorders, adult onset v3.29 LAMB1 Achchuthan Shanmugasundram Classified gene: LAMB1 as Amber List (moderate evidence)
Neurodegenerative disorders, adult onset v3.29 LAMB1 Achchuthan Shanmugasundram Gene: lamb1 has been classified as Amber List (Moderate Evidence).
Neurodegenerative disorders, adult onset v3.28 LAMB1 Achchuthan Shanmugasundram reviewed gene: LAMB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly 5, OMIM:615191; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neurodegenerative disorders, adult onset v3.4 LAMB1 Eleanor Williams reviewed gene: LAMB1: Rating: ; Mode of pathogenicity: ; Publications: 34606115; Phenotypes: Cerebral small vessel disease, with leukoencephalopathy and hippocampal memory impairment; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Neurodegenerative disorders, adult onset v3.3 LAMB1 Eleanor Williams gene: LAMB1 was added
gene: LAMB1 was added to Neurodegenerative disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: LAMB1 was set to