Severe microcephalyGene: AP4B1
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 list
Created: 30 Aug 2020, 5:45 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Spastic paraplegia 47, autosomal recessive, MIM# 614066
Variants in this GENE are reported as part of current diagnostic practice
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