Undiagnosed Phenylketonuria Can Exist Everywhere: Results From an International Survey

peer reviewedMany countries do not have a newborn screening (NBS) program, and immigrants from such countries are at risk for late diagnosis of phenylketonuria (PKU). In this international survey, 52 of 259 patients (20%) with late diagnosed PKU were immigrants, and 145 of the 259 (55%) were born before NBS or in a location without NBS. © 2021 The Author

Altered Visual Experience Induces Instructive Changes of Orientation Preference in Mouse Visual Cortex

Stripe rearing, the restriction of visual experience to contours of only one orientation, leads to an overrepresentation of the experienced orientation among neurons in the visual cortex. It is unclear, however, how these changes are brought about. Are they caused by silencing of neurons tuned to non-experienced orientations, or do some neurons change their preferred orientation? To address this question, we stripe-reared juvenile mice using cylinder lens goggles. Following stripe rearing, the orientation preference of cortical neurons was determined with two-photon calcium imaging. This allowed us to sample all neurons in a given field of view, including the non-responsive ones, thus overcoming a fundamental limitation of extracellular electrophysiological recordings. Stripe rearing for 3 weeks resulted in a clear overrepresentation of the experienced orientation in cortical layer 2/3. Closer inspection revealed that the stripe rearing effect changed with depth in cortex: The fraction of responsive neurons decreased in upper layer 2/3, but changed very little deeper in this layer. At the same time, the overrepresentation of the experienced orientation was strongest in lower layer 2/3. Thus, diverse mechanisms contribute to the overall stripe rearing effect, but for neurons in lower layer 2/3 the effect is mediated by an instructive mechanism, which alters the orientation tuning of individual neurons

Whole Xp Deletion in a Girl with Mental Retardation, Epilepsy, and Biochemical Features of OTC Deficiency

Background: Females with a total or partial deletion of the short arm of the X chromosome have variable features of Turner syndrome, but mental retardation (MR) rarely occurs. The haploinsufficiency of deleted genes that escape X-inactivation may explain the occurrence of MR and autism. Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder and is inherited in an X-linked semi-dominant trait, and the OTC gene maps to Xp21. Methods: We report on a girl with MR, epilepsy and biochemical changes characteristic of OTC deficiency but no identifiable point mutation in the OTC gene. Standard G-banding cytogenetic analysis, whole genome karyotyping, and X-inactivation studies were performed to determine the genetic etiology of the OTC deficiency in the patient. Results: Cytogenetic analysis and molecular karyotyping using SNP array revealed a deletion of the whole short arm of the X chromosome (Xp22.33–p11.1). Inactivation studies also revealed a completely skewed X-inactivation. Conclusion: Our patient presented with MR, epilepsy, and some evidence of reduced OTC activity, but performed genetic studies gave no explanation for this phenotype. We hope that this case report contributes to the understanding of the underlying genetic factors of the manifestation of X-linked disorders in female patients