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Intellectual disability - microarray and sequencing v4.28 TUBB2B Arina Puzriakova Phenotypes for gene: TUBB2B were changed from Polymicrogyria, symmetric or asymmetric, 610031; POLYMICROGYRIA ASYMMETRIC (PMGA) to Cortical dysplasia, complex, with other brain malformations 7, OMIM:610031
Intellectual disability - microarray and sequencing v3.696 TUBB2A Arina Puzriakova Publications for gene: TUBB2A were set to 24702957
Intellectual disability - microarray and sequencing v3.695 TUBB2A Arina Puzriakova Phenotypes for gene: TUBB2A were changed from CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 5 to Cortical dysplasia, complex, with other brain malformations 5, OMIM:615763; Complex cortical dysplasia with other brain malformations 5, MONDO:0014337
Intellectual disability - microarray and sequencing v3.209 TUBB2A Arina Puzriakova reviewed gene: TUBB2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32571897; Phenotypes: Cortical dysplasia, complex, with other brain malformations 5, 615763; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability - microarray and sequencing v2.876 MED12L Eleanor Williams Added comment: Comment on list classification: Rating Amber. CNVs encompass other genes. Two cases with SNVs have moderate/severe ID and one of these also has a VUS in TUBB2B. The other two SNV cases have mild ID.
Intellectual disability - microarray and sequencing v2.550 UFM1 Konstantinos Varvagiannis gene: UFM1 was added
gene: UFM1 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: UFM1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: UFM1 were set to 28931644; 29868776
Phenotypes for gene: UFM1 were set to Leukodystrophy hypomyelinating 14, 617899
Penetrance for gene: UFM1 were set to Complete
Review for gene: UFM1 was set to GREEN
Added comment: Biallelic UFM1 mutations cause Leukodystrophy hypomyelinating 14, MIM 617899.

PMID: 28931644 is the first report on 16 individuals from 14 families with shared Roma ethnic background. All subjects were found to harbor a UFM1 promoter 3 basepair deletion in the homozygous state.

All patients demonstrated a severe phenotype including lack of development and severe epileptic encephalopathy while their MRI images demonstrated hypomyelination with atrophy of the basal ganglia and the cerebellum.

The promoter deletion was detected by exome sequencing. Previously a 0.8 Mb homozygous region was identified to be shared by all the patients in whom a SNP array was performed. Alternative causes, notably TUBB4A mutations and deletions/duplications were excluded. 3 individuals had Sanger sequencing of all coding regions within the homozygous interval to rule out other - eventually missed - variants.

PMID: 29868776 reports 4 additional individuals from 2 consanguineous families (one from Ethiopia, for the other this was not specified). All 4 patients were homozygous for the c.241C>T (NM_016617.3) or p.(Arg81Cys) variant which was shown to be hypomorphic upon functional studies.

The phenotype consisted of developmental delay (4/4 or 20/20 including the patients from the previous report with which comparison is made in table 2 of the article) with microcephaly (4/4 or 20/20) and seizures (4/4 or 16/20) as well as MRI abnormalities. Failure to thrive and/or short stature were also among the most common features.

UFM1 (as well as UFC1 also discussed in the same article) participate in ufmylation, with mutations in other enzymes of the same process (notably UBA5 - gene rated Green in the ID and epilepsy panels) having already been described in neurodevelopmental disorders.

As a result, this gene can be considered for inclusion in this panel as green (or amber).
Sources: Literature, Expert Review
Intellectual disability - microarray and sequencing v2.468 TUBB3 Louise Daugherty Source Victorian Clinical Genetics Services was added to TUBB3.
Intellectual disability - microarray and sequencing v2.468 TUBB2B Louise Daugherty Source Victorian Clinical Genetics Services was added to TUBB2B.
Intellectual disability - microarray and sequencing v2.468 TUBB2A Louise Daugherty Source Victorian Clinical Genetics Services was added to TUBB2A.
Intellectual disability - microarray and sequencing TUBB4A BRIDGE consortium edited their review of TUBB4A
Intellectual disability - microarray and sequencing TUBB2B BRIDGE consortium edited their review of TUBB2B
Intellectual disability - microarray and sequencing TUBB2A BRIDGE consortium edited their review of TUBB2A
Intellectual disability - microarray and sequencing TUBB BRIDGE consortium edited their review of TUBB
Intellectual disability - microarray and sequencing TUBB4A BRIDGE consortium edited their review of TUBB4A
Intellectual disability - microarray and sequencing TUBB2B BRIDGE consortium edited their review of TUBB2B
Intellectual disability - microarray and sequencing TUBB2A BRIDGE consortium edited their review of TUBB2A
Intellectual disability - microarray and sequencing TUBB BRIDGE consortium edited their review of TUBB
Intellectual disability - microarray and sequencing TUBB4A BRIDGE consortium reviewed TUBB4A
Intellectual disability - microarray and sequencing TUBB2B BRIDGE consortium reviewed TUBB2B
Intellectual disability - microarray and sequencing TUBB2A BRIDGE consortium reviewed TUBB2A
Intellectual disability - microarray and sequencing TUBB BRIDGE consortium reviewed TUBB