Severe microcephaly
Gene: AP4B1Comment from NHS Genomic Medicine Service: primary presentation is ID/DD/spasticity/hypotonia: green on ID and HSP and hypotonic infant panels - not clear if severe microephaly exists in absence of theseCreated: 10 Mar 2022, 10:52 a.m. | Last Modified: 10 Mar 2022, 10:52 a.m.
Panel Version: 2.282
After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed.Created: 10 Mar 2022, 10:52 a.m. | Last Modified: 10 Mar 2022, 10:52 a.m.
Panel Version: 2.282
Comment on list classification: New gene added by Zornitza Stark. Rating Amber but will be flagged for review at the next GMS panel update to assess whether clinical utility is sufficient for inclusion as Green (added 'for-review' tag).
Literature search revealed at least 24 unrelated published cases with biallelic variants in this gene. Microcephaly is commonly reported but often mild, and particularly in the context of other more prominent/universal features (ID, HSP, etc) this disorder may be better represented by other panels.
Nonetheless, microcephaly of relevant severity to this panel (OFC ≤ -3 SD) has been recorded in at least 8 unrelated families which reaches the threshold for inclusion (PMIDs: 21620353; 29193663; 30337681; 32166732)Created: 5 Jan 2021, 1:15 p.m. | Last Modified: 5 Jan 2021, 1:15 p.m.
Panel Version: 2.60
Microcephaly is an early, prominent presenting feature of this progressive neurological disorder. At least 4 unrelated families reported.
Sources: Expert listCreated: 30 Aug 2020, 5:45 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spastic paraplegia 47, autosomal recessive, MIM# 614066
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag for-review was removed from gene: AP4B1.
Phenotypes for gene: AP4B1 were changed from Spastic paraplegia 47, autosomal recessive, MIM# 614066 to Spastic paraplegia 47, autosomal recessive, OMIM:614066; Hereditary spastic paraplegia 47, MONDO:0013551
Publications for gene: AP4B1 were set to 21620353; 22290197; 24700674; 24781758
Gene: ap4b1 has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: AP4B1.
gene: AP4B1 was added gene: AP4B1 was added to Severe microcephaly. Sources: Expert list Mode of inheritance for gene: AP4B1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AP4B1 were set to 21620353; 22290197; 24700674; 24781758 Phenotypes for gene: AP4B1 were set to Spastic paraplegia 47, autosomal recessive, MIM# 614066 Review for gene: AP4B1 was set to GREEN gene: AP4B1 was marked as current diagnostic