Intellectual disability - microarray and sequencing
Gene: MAP1BThe rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 14 Mar 2022, 2:22 p.m. | Last Modified: 14 Mar 2022, 2:22 p.m.
Panel Version: 3.1519
MAP1B was flagged by a GLH following identification of some potential cases relating to variants in this gene and predominantly ID phenotypes within 100K data. Although these are pending confirmations (will request update once cases are validated), upon reassessment of MAP1B it was highlighted that inclusion on this panels may still be warranted to increase the likelihood of detecting cases, particularly given that DD/ID is more likely to be observed earlier in the course of disease albeit at varying severities.
For this reason, MAP1B should be promoted to Green status at the next GMS panel review (tagged Q3_21_rating)Created: 1 Sep 2021, 2:35 p.m. | Last Modified: 1 Sep 2021, 2:35 p.m.
Panel Version: 3.1249
Comment on list classification: Maintaining Amber rating as although cognitive impairment is reported in multiple (but not all) cases, often this is mild and not sufficient for a clinical diagnosis of ID. Affected individuals are more likely to be assessed in view of the brain malformations - MAP1B will be added to the 'Malformations of cortical development' panel.Created: 11 Nov 2020, 1:41 p.m. | Last Modified: 11 Nov 2020, 1:41 p.m.
Panel Version: 3.513
Associated with 'Periventricular nodular heterotopia 9' in OMIM, but currently not in Gene2Phenotype.
PMID: 30150678 (2018) - Three Icelandic families with different predicted LoF variants in MAP1B, with periventricular nodular heterotopia (PVNH), decreased volume of the white matter and corpus callosum, and variable ID (as described previously in review by Konstantinos Varvagiannis).
PMID: 29738522 (2018) - Five individuals from four families all with PVNH, and some with seizures, cognitive impairment, and other dysmorphic features. Only one patient had ID with a full-scale IQ of 55. Two individuals presented some learning difficulties and two had normal cognitive function.
PMID: 31317654 (2019) - One patient with a de novo MAP1B variant and PVNH, dysgenesis of corpus callosum, ID/GDD, microcephaly, short stature, mild conductive hearing loss, focal epilepsy, and dysmorphic featuresCreated: 11 Nov 2020, 1:19 p.m. | Last Modified: 11 Nov 2020, 1:19 p.m.
Panel Version: 3.510
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Periventricular nodular heterotopia 9, 618918
Publications
More than five families recently described with mono allelic variants in this gene, intellectual disability and variable other features including brain malformations.Created: 6 Mar 2020, 10:03 a.m. | Last Modified: 6 Mar 2020, 10:03 a.m.
Panel Version: 3.3
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Intellectual disability; seizures; PVNH; dysmorphic features
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: New gene added by external expert and reviewed by curation team. MAP1B has been given an amber gene rating based on the evidence provided by the expert review. It is not associated with any phenotype on OMIM or Gene2Phenotype.Created: 18 Feb 2019, 1:07 p.m.
In PMID 30150678 the authors report on a family with 5 individuals diagnosed with intellectual disability (ID, IQ <= 70 and associated impairments in adaptive function) and 3 further relatives with IQ below 70, not fulfilling the criteria for a clinical diagnosis of ID. A frameshift variant in MAP1B segregated with the ID/low IQ phenotype. This variant was not found in 31463 Icelanders for whom whole genome sequencing data were available.
The authors confirmed association of MAP1B loss-of-function (LoF) variants by demonstrating the presence of 2 other stopgain mutations in 2 further families. Among the 6 mutation carriers in these families, the average IQ was 81 with 2 of these subjects fulfilling the criteria for intellectual disability. 3 of the 6 mutation carriers had a diagnosis of autism spectrum disorder. Carriers demonstrated 24% less white matter volume (-2.1 SD) and 47% less corpus callosum volume (-2.4 SD) compared to controls.
Mean full-scale IQ, performance IQ and verbal IQ were 68.3 (with a SD of 10.5), 66.4 (SD of 9.3) and 74.5 (SD of 14.8) in MAP1B LoF carriers.
All 3 LoF variants reported result in a truncated but stable MAP1B protein as demonstrated by western blot analysis.
MAP1B undergoes post-translational modification and is cleaved (at position 2206) into a heavy chain and a light chain. The authors note that all LoF variants lead to truncation prior to the cleavage site.
As commented by the authors, LoF variants are found in publicly available databases at a frequency of approx. 1 in 10000.
One individual with de novo frameshift variant in Decipher ( https://decipher.sanger.ac.uk/search?q=gene%3AMAP1B#research-variants/results ).
De novo and inherited MAP1B variants have previously been described in individuals with periventricular nodular heterotopia (PMID: 29738522). This was also a feature in 9 individuals in the previous ID study.
Although PMID 30150678 is entitled "MAP1B mutations cause intellectual disability and extensive white matter deficit", intellectual disability was not a feature in all individuals or was rather mild when present.
Sources: Literature, Expert ReviewCreated: 12 Oct 2018, 10:27 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Intellectual disability
Publications
Tag Q3_21_rating was removed from gene: MAP1B.
Source Expert Review Green was added to MAP1B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q3_21_rating tag was added to gene: MAP1B.
Gene: map1b has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: MAP1B were changed from Intellectual disability; No OMIM number to Periventricular nodular heterotopia 9, 618918
Publications for gene: MAP1B were set to 30150678; 29738522
Gene: map1b has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: MAP1B were changed from Intellectual disability to Intellectual disability; No OMIM number
gene: MAP1B was added gene: MAP1B was added to Intellectual disability. Sources: Literature,Expert Review Mode of inheritance for gene: MAP1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAP1B were set to 30150678; 29738522 Phenotypes for gene: MAP1B were set to Intellectual disability Penetrance for gene: MAP1B were set to unknown Review for gene: MAP1B was set to AMBER