Severe microcephalyGene: PLAA
Comment on list classification: Added PLAA to panel based on progressive microcephaly phenotypes recorded in 2 papers (PMID:28007986 and PMID:28413018) and association with MIM:617527. However microcephaly was not consistently reported at birth, and based on current reports the phenotype isn't severe enough to be considered as a green gene for this panel.
Created: 28 Aug 2017, 9:42 a.m.
In 7 infants from 3 consanguineous Pakistani families with a lethal form of NDMSBA, Hall et al. (2017, PMID:28413018) identified a homozygous missense mutation in the PLAA gene (G23V). Haplotype analysis indicated a common founder rather than a recurrent mutation. Microcephaly developed in the first year- OFC of affected individuals varies between - and -4 at birth, and progresses to -3 to -6 after 1 year (Figure 1F). Microcephaly also seen in mouse model.
Created: 28 Aug 2017, 9:40 a.m.
In 7 patients from 2 consanguineous Israeli families with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (NDMSBA, MIM:617527), Falik Zaccai et al. (2017, PMID:28007986) identified a homozygous missense mutation in the PLAA gene (L752F). The variant was found in a heterozygous state in 3 of 92 residents from the local village. Haplotype analysis indicated a common ancestral haplotype in the 2 families. Head circumference was normal at birth and decreased to >2 SD below mean in the ensuing years. In 2 patients, they observed an unexplained gradual increase in head circumference up to 75% after the age of 5 years.
Created: 28 Aug 2017, 9:39 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, 617527
This gene has been classified as Red List (Low Evidence).
Publications for PLAA were set to 28007986; 28413018
PLAA was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Other
PLAA was created by rfoulger