A case of Ververi-Brady syndrome due to QRICH1 loss of function and the literature review.

Ververi-Brady syndrome (VBS), first reported in 2018, is characterized by intellectual disability, speech delay, and mild dysmorphic facial features. VBS has been linked to de novo loss-of-function variants in the glutamine-rich protein 1 (QRICH1) on chromosome 3p21 and was reported until lately in only five individuals. Four additional cases have just been described substantiating the notion that children with VBS are mildly dysmorphic, mildly to moderately intellectually disabled, have linear growth shortage, are picky eaters, and have notable attention and social behavioral deficits. We describe a new patient and review the clinical and genetic information, on all previously reported VBS cases. The child here reported is noted for maladaptive behavior, sensory hypersensitivity, and slow linear growth. He is mainly hyperactive, distractible, impulsive, and inattentive. His speech, initially delayed, is fair and his verbal comprehension age adequate.

Frequency of canine nt230(del4) MDR1 mutation in prone pure breeds, their crosses and mongrels in Israel - insights from a worldwide comparative perspective.

BACKGROUND: Sensitivity to macrocyclic lactones, which are commonly used in veterinary clinics, was first found in Rough Collies, and was attributed in 2001 to a 4 bp deletion in the MDR1 gene. The list of affected breeds currently includes 13 breeds. Researchers from different countries and continents examined the allelic frequencies of the nt230(del4) MDR1 mutation, emphasizing the clinical importance of this test not only to mutation-prone dogs, but also to their crosses and mongrels, since treatment of a deletion carrier with these compounds may lead to its death. In this study, the allelic frequencies of nt230(del4) MDR1 mutation in affected breeds, their crosses, unrelated pure breeds and mongrels are reported for the state of Israel (n = 1416 dogs). The Israeli data were compared with reports from the US, Europe, UK, Australia and Japan. RESULTS: The allelic frequencies of nt230(del4) MDR1 mutation in Israel for Australian, Swiss and German Shepherds (31%, 17% and 2.4%, respectively) are similar to the corresponding frequencies worldwide, much higher for Border Collies (4.8%), twice lower for Rough Collies (28%, compared to 55% or more elsewhere), and ~1% for mongrels. The frequencies for crosses of Australian Shepherd and Border Collies in Israel are 4 and 1.6 times lower, respectively, compared to the frequencies for the respective pure breeds. CONCLUSIONS: This work, that for the first time presents the frequency of nt230(del4) MDR1 mutation in Israel, along with a worldwide survey, has implications for clinicians, owners and breeders of sheepdogs and their crosses and supports the need for extra care in treatment and in future breeding. Of note, the relative proportion of affected breeds, in the overall tested dogs, might be higher than their actual proportion in Israel due to directed samples collection by veterinarians for clinical purposes, as these are mainly limited to certain affected breeds or dogs that resemble them.