Proliferative visceral <Emphasis Type="Italic">Isospora</Emphasis> (atoxoplasmosis) with morbid impact on the Israeli sparrow <Emphasis Type="Italic">Passer domesticus biblicus</Emphasis> Hartert, 1904

House sparrows (Passer domesticus biblicus Hartert, 1904) caught in the Jordan valley, the coastal plain, and the desert region in Southern Israel were found massively infected with extraintestinal proliferative stages of Isospora, previously named Atoxoplasma. Infection coincided with Isospora spp. infections in the digestive tract. Prevalence of infection reached 70% among sparrows of all three regions; however, only in the Jordan valley did the severity of the sparrows compromised their survival. Healthy appearing captured birds showed symptoms of "going light" syndrome -- diarrhea, emaciation, and death. Birds succumbed within 48 h to 15 days after confinement to cages. Merozoites accumulated predominantly in the spleen but were rarely found in the peripheral blood. The parasite stages in the visceral leukocytes propagated by merogony and yielded single large waiting-stage merozoites. Visceral infections resulted in multifocal necrosis. Proliferative visceral Isospora infection (atoxoplasmosis) is one of the more severe causes of mortality among captive birds, free-ranging birds appear to coexist with the infection but succumb under capture stress.     

Bi-allelic PAGR1 variants are associated with microcephaly and a severe neurodevelopmental disorder: Genetic evidence from two families

Exome and genome sequencing were used to identify the genetic etiology of a severe neurodevelopmental disorder in two unrelated Ashkenazi Jewish families with three affected individuals. The clinical findings included a prenatal presentation of microcephaly, polyhydramnios and clenched hands while postnatal findings included microcephaly, severe developmental delay, dysmorphism, neurologic deficits, and death in infancy. A shared rare homozygous, missense variant (c.274A > G; p.Ser92Gly, NM_024516.4) was identified in PAGR1, a gene currently not associated with a Mendelian disease. PAGR1 encodes a component of the histone methyltransferase MLL2/MLL3 complex and may function in the DNA damage response pathway. Complete knockout of the murine Pagr1a is embryonic-lethal. Given the available evidence, PAGR1 is a strong candidate gene for a novel autosomal recessive severe syndromic neurodevelopmental disorder.