We have identified a three-generation pedigree segregating a novel mutation in the ACTG1 gene that causes Baraitser-Winter Syndrome with extremely variable expressivity, leading to an initial diagnosis of isolated AD hearing loss in two members.
In addition to that, the recent discovery of missense mutations in one of the two ubiquitously expressed cytoplasmic β- and γ-acting-encoding genes ACTB (7p22.1) and ACTG1 (17q25.3) in patients carrying a clinical diagnosis of BWSM, FA, or CCF has provided further evidence that these clinical conditions do indeed belong to the same entity at the molecular level.
Taken together, we expand the clinical spectrum of the ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome demonstrating the mild end of the facial and brain manifestations.
Baraitser-Winter, Fryns-Aftimos and cerebrofrontofacial syndrome types 1 and 3 have recently been associated with heterozygous gain-of-function mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1 that encode β- and γ-actins.
Our results highlight the powerful diagnostic value of exome sequencing for patients with microlissencephaly, that may expand the malformation spectrum of ACTG1-related Baraitser-Winter cerebrofrontofacial syndrome and may suggest that ACTG1 could be added to the list of genes for assessing microlissencephaly.
ACTB and ACTG1 mutations have recently been reported to cause Baraitser-Winter syndrome (BRWS) - a rare condition characterized by ptosis, colobomata, neuronal migration disorder, distinct facial anomalies and intellectual disability.
Recent work in Baraitser-Winter syndrome has identified ACTB and ACTG1 mutations in a cohort of individuals, and we rediagnosed the patient with atypical Baraitser-Winter syndrome.