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Severe microcephaly

Gene: AP4M1

Amber List (moderate evidence)

AP4M1 (adaptor related protein complex 4 mu 1 subunit)
EnsemblGeneIds (GRCh38): ENSG00000221838
EnsemblGeneIds (GRCh37): ENSG00000221838
OMIM: 602296, Gene2Phenotype
AP4M1 is in 9 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Microcephaly is a variable feature of the disease presentation - often too mild relative to the scope of this panel, or absent altogether. However, there are at least 3 unrelated cases with sufficiently severe microcephaly. Although the overall disorder may be better represented by other panels (e.g. HSP, ID) for which this gene is already Green, microcephaly can be an early manifestation that may be evident prior to other AP4M1-related phenotypes. Therefore, there may be value in inclusion on this panel.

Rating Amber, with recommendation of review by the GMS team to assess whether there is sufficient evidence to support a Green rating on this panel (added 'for-review' tag)
Created: 27 Jan 2021, 1:31 p.m. | Last Modified: 27 Jan 2021, 1:31 p.m.
Panel Version: 2.86
Well established association with a HSP phenotype - also listed in OMIM and Gene2Phenotype.

Multiple families reported where microcephaly is a feature (PMID:19559397; 21937992; 24700674; 25496299; 28464862; 29473051; 32337850). Degree of microcephaly is not always indicated but at least 3 unrelated individuals (PMID:24700674; 28464862) did present with relevant severity to this panel (HC ≤ -3 SD). Reported as prenatal/early onset presentation.
Created: 27 Jan 2021, 1:31 p.m. | Last Modified: 27 Jan 2021, 1:31 p.m.
Panel Version: 2.85

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic paraplegia 50, autosomal recessive, OMIM:612936

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Despite the OMIM name, this is a complex neurological condition, where microcephaly is an early prominent presenting feature.

PMID: 28464862;
- 1x with severe progressive microcephaly (< - 4 SD)
- homozygous nonsense

PMID: 24700674;
- 2x unrelated patients (1 and 3) < -3 SD head circumference
- 2x homozygous nonsense
Sources: Expert list
Created: 31 Aug 2020, 11:03 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic paraplegia 50, autosomal recessive (MIM#612936)

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Spastic paraplegia 50, autosomal recessive, OMIM:612936
  • Hereditary spastic paraplegia 50, MONDO:0013048
Tags
for-review
OMIM
602296
Clinvar variants
Variants in AP4M1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

27 Jan 2021, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: AP4M1 were changed from Spastic paraplegia 50, autosomal recessive (MIM#612936) to Spastic paraplegia 50, autosomal recessive, OMIM:612936; Hereditary spastic paraplegia 50, MONDO:0013048

27 Jan 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: ap4m1 has been classified as Amber List (Moderate Evidence).

27 Jan 2021, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: AP4M1.

31 Aug 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

gene: AP4M1 was added gene: AP4M1 was added to Severe microcephaly. Sources: Expert list Mode of inheritance for gene: AP4M1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AP4M1 were set to 28464862; 24700674 Phenotypes for gene: AP4M1 were set to Spastic paraplegia 50, autosomal recessive (MIM#612936) Review for gene: AP4M1 was set to GREEN gene: AP4M1 was marked as current diagnostic