Severe microcephalyGene: SMARCA5
Comment on list classification: New gene added and reviewed Green by Julia Baptista (RD&E NHS FT). SMARCA5 should be promoted to Green at the next GMS panel update.
Variants have been associated with a variable neurodevelopmental phenotype including predominantly mild DD, short stature, and microcephaly (PMID:33980485). Postnatal microcephaly [HC ranging between -2.33 and -6.21 SD] was evident in 10/12 individuals, and three had a birth HC less than −2.5 SD. Overall sufficient number of unrelated families presenting microcephaly of relevant severity to warrant a Green rating on this panel.
Created: 9 Jun 2021, 3:12 p.m. | Last Modified: 9 Jun 2021, 3:33 p.m.
Panel Version: 2.207
The authors identified seven missense variants, one splice-altering variant that led to exon skipping and in-frame deletion, and one recurrent in-frame deletion in 12 individuals from
10 unrelated families. The variant was de novo in nine individuals. They presented a broad range of clinical features from isolated autism to syndromic intellectual disability.
Created: 1 Jun 2021, 10:27 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
intellectual disability; postnatal microcephaly; hypotonia; failure to thrive
Tag Q2_21_NHS_review was removed from gene: SMARCA5.
gene: SMARCA5 was added gene: SMARCA5 was added to Severe microcephaly. Sources: Literature,Expert Review Amber Q2_21_rating, Q2_21_NHS_review tags were added to gene: SMARCA5. Mode of inheritance for gene: SMARCA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SMARCA5 were set to 33980485 Phenotypes for gene: SMARCA5 were set to intellectual disability; postnatal microcephaly; hypotonia; failure to thrive Penetrance for gene: SMARCA5 were set to unknown