Identification of the first homozygous intragenic deletion in the YY1AP1 gene in a consanguineous family: New insights into the phenotypic variability associated with Grange syndrome.

Grange syndrome (GRNG-MIM#135580) is a rare recessive disorder associating variable features including diffuse vascular stenosis, brachysyndactyly, osteopenia with increased bone fragility, cardiac malformations, and variable developmental delay. Since its first description in 1998, only 15 individuals from 10 families have been reported, carrying homozygous or compound heterozygous frameshift or nonsense variants in YY1AP1. In a patient with cutaneous and bone syndactyly and a hemorrhagic stroke at the age of 16 months, consistent with a clinical diagnosis of GRNG, we performed exome sequencing after negative array-CGH and congenital limb malformation panel results. Copy number variant analysis from exome data identified a homozygous intragenic out-of-frame deletion of 1.84 kb encompassing exons seven and eight of YY1AP1, confirming a molecular diagnosis of GRNG. Genetic counseling led to the identification of additional family members compatible with GRNG. Here, we provide new insights into the phenotypic variability associated with GRNG and highlight the utility of the detection of small copy number variants to identify the molecular causes of heterogeneous malformative genetic disorders.

The faces of development: a review of early face processing over childhood.

The understanding of the adult proficiency in recognizing and extracting information from faces is still limited despite the number of studies over the last decade. Our knowledge on the development of these capacities is even more restricted, as only a handful of such studies exist. Here we present a combined reanalysis of four ERP studies in children from 4 to 15 years of age and adults (n = 424, across the studies), which investigated face processing in implicit and explicit tasks. We restricted these analyses to what was common across studies: early ERP components and upright face processing across all four studies and the inversion effect, investigated in three of the studies. These data demonstrated that processing faces implicates very rapid neural activity, even in young children--at the P1 component--with protracted age-related change in both P1 and N170, that were sensitive to the different task demands. Inversion produced latency and amplitude effects on the P1 from the youngest group, but on N170 only starting in mid childhood. These developmental data suggest that there are functionally different sources of the P1 and N170, related to the processing of different aspects of faces.

Direction of gaze effects on early face processing: eyes-only versus full faces.

The N170 event-related potential (ERP) reflects an early stage of face processing. We wished to determine if it would also index the intuitively important information provided by direction of gaze. Two studies were run. In one, stimuli included full faces with the eyes looking forward, to the left or closed; in the other study the stimuli included eyes-only, looking forward, left or closed. Gaze direction had no effects on amplitude, but longer latencies were found for faces with eyes closed. With eyes-only stimuli, more marked effects on latencies and borderline effects on amplitudes were seen. We suggest that there can only be limited evidence of gaze-specific sensitivity in ERP studies in humans, without eye movement.