Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections.

PURPOSE: We sought to delineate a multisystem disorder caused by recessive cysteine-rich with epidermal growth factor-like domains 1 (CRELD1) gene variants. METHODS: The impact of CRELD1 variants was characterized through an international collaboration utilizing next-generation DNA sequencing, gene knockdown, and protein overexpression in Xenopus tropicalis, and in vitro analysis of patient immune cells. RESULTS: Biallelic variants in CRELD1 were found in 18 participants from 14 families. Affected individuals displayed an array of phenotypes involving developmental delay, early-onset epilepsy, and hypotonia, with about half demonstrating cardiac arrhythmias and some experiencing recurrent infections. Most harbored a frameshift in trans with a missense allele, with 1 recurrent variant, p.(Cys192Tyr), identified in 10 families. X tropicalis tadpoles with creld1 knockdown displayed developmental defects along with increased susceptibility to induced seizures compared with controls. Additionally, human CRELD1 harboring missense variants from affected individuals had reduced protein function, indicated by a diminished ability to induce craniofacial defects when overexpressed in X tropicalis. Finally, baseline analyses of peripheral blood mononuclear cells showed similar proportions of immune cell subtypes in patients compared with healthy donors. CONCLUSION: This patient cohort, combined with experimental data, provide evidence of a multisystem clinical syndrome mediated by recessive variants in CRELD1.

Description of a new species of Liropus (Crustacea, Amphipoda) from Puerto Vallarta, Pacific coast of Mexico.

A new species of the genus Liropus Mayer, 1920 (Amphipoda, Caprellidae) is described from the Mexican Tropical Pacific coast. Liropus alarconi n. sp. is described on the basis of four specimens collected in association with the tropical marine sponge Trikentrion helium Dickinson, 1945, near to coralline patches, between 2330 m depth. Liropus alarconi n. sp. can be distinguished from its congeners for the following characters: pereonites 25 each with one dorsodistal projection and pereonite 3 with a mediolateral projection.

A new species of Deutella Mayer 1890 (Crustacea: Amphipoda) from the Mexican Pacific coast.

A new species of caprellid, Deutella mazatlanensis n. sp., is described from Mazatlán Bay, (east Pacific México). Deutella mazatlanensis was found associated with bryozoans, hydroids and sponges in shallow waters. The new species can be differentiated from the remaining species of the genus mainly by the dorsal, anteriorly directed projection on the head; the two dorsal projections and a lateral acute projection anteroventrally projected on pereonite 2 and gnathopod 2 in males. The presence of this species on the Mexican Pacific coast, constitutes the fourth report of Deutella genus for the Pacific Ocean and the first record from the tropical Eastern Pacific.