Severe microcephaly
Gene: ARPC4
The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.Created: 10 Oct 2023, 2:56 p.m. | Last Modified: 10 Oct 2023, 2:56 p.m.
Panel Version: 4.33
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Comment on list classification: There is sufficient evidence for this gene to be rated GREEN at the next GMS review.Created: 31 May 2023, 12:01 p.m. | Last Modified: 31 May 2023, 12:01 p.m.
Panel Version: 4.17
As reviewed by Zornitza Stark, PMID:35047857 reported seven cases from six unrelated families with the same missense variant (p.Arg158Cys) and presenting with developmental and speech delays, of which six individuals from five families presented with microcephaly. Three individuals from two of these families had severe microcephaly with occipitofrontal circumference (OFC) beyond 3 standard deviations below the mean for age. In addition, functional studies showed that the variant is associated with a decreased amount of F-actin in cells from two affected individuals.
This gene has been associated with relevant phenotypes in both OMIM (MIM #620141) and Gene2Phenotype (ARPC4-related microcephaly and developmental delay with 'strong' rating in the DD panel).Created: 31 May 2023, noon | Last Modified: 31 May 2023, noon
Panel Version: 4.14
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Developmental delay, language impairment, and ocular abnormalities, OMIM:620141; microcephaly, MONDO:0001149
Publications
7 affected individuals from 6 families (gonadal mosaicism was confirmed in the mother of the 2 affected siblings) with a recurrent missense variant (NM_005718.4:c.472C>T; p.R158C). 6/7 affected individuals had microcephaly. The variant was associated with a decreased amount of F-actin in cells from two affected individuals.
Sources: LiteratureCreated: 4 Dec 2021, 2:49 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Microcephaly; mild motor delays; significant speech impairment
Publications
Tag Q2_23_promote_green was removed from gene: ARPC4.
Source Expert Review Green was added to ARPC4. Source NHS GMS was added to ARPC4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q2_23_promote_green tag was added to gene: ARPC4.
Gene: arpc4 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: ARPC4 were changed from Microcephaly; mild motor delays; significant speech impairment to Developmental delay, language impairment, and ocular abnormalities, OMIM:620141; microcephaly, MONDO:0001149
Publications for gene: ARPC4 were set to DOI:https://doi.org/10.1016/j.xhgg.2021.100072
gene: ARPC4 was added gene: ARPC4 was added to Severe microcephaly. Sources: Literature Mode of inheritance for gene: ARPC4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ARPC4 were set to DOI:https://doi.org/10.1016/j.xhgg.2021.100072 Phenotypes for gene: ARPC4 were set to Microcephaly; mild motor delays; significant speech impairment Review for gene: ARPC4 was set to GREEN