Congenital coenzyme Q5-linked pathology: causal genetic association, core phenotype, and molecular mechanism.

Coenzyme Q5 (COQ5), a C-methyltransferase, modifies coenzyme Q10 (COQ10) during biosynthesis and interacts with polyA-tail regulating zinc-finger protein ZC3H14 in neural development. Here, we present a fifth patient (a third family) worldwide with neurodevelopmental and physiological symptoms including COQ10 deficiency. Our patient harbors one novel c.

A Zebrafish/Drosophila Dual System Model for Investigating Human Microcephaly.

Microcephaly presents in neurodevelopmental disorders with multiple aetiologies, including bi-allelic mutation in , a component of the biologically fundamental and conserved microtubule-nucleation complex, γ-TuRC. Elucidating underlying principles driving microcephaly requires clear phenotype recapitulation and assay reproducibility, areas where go-to experimental models fall short. We present an alternative simple vertebrate/invertebrate dual system to investigate fundamental -related processes driving human microcephaly and associated developmental traits.

De Novo Variant Expands the Phenotype and Genotype of Partial Deafness and Baraitser-Winter Syndrome.

Actin molecules are fundamental for embryonic structural and functional differentiation; γ-actin is specifically required for the maintenance and function of cytoskeletal structures in the ear, resulting in hearing. Baraitser-Winter Syndrome (B-WS, OMIM #243310, #614583) is a rare, multiple-anomaly genetic disorder caused by mutations in either cytoplasmically expressed actin gene, (β-actin) or (γ-actin). The resulting actinopathies cause characteristic cerebrofrontofacial and developmental traits, including progressive sensorineural deafness.

A Patient with Berardinelli-Seip Syndrome, Novel Splicesite Mutation and Concomitant Development of Non-diabetic Polyneuropathy.

Primary polyneuropathy in the context of Seip-Berardinelli type 1 seipinopathy, or congenital generalized lipodystrophy type 1 (CGL1) has not been previously reported. We report the case history of a 27 year old female CGL1 patient presenting with an unusual additional development of non-diabetic peripheral neuropathy and learning disabilities in early adolescence. Whole exome sequencing (WES) of the patient genome identified a novel variant, homozygous for a 52 bp intronic deletion in the locus, coding for 1-acylglycerol-3-phosphate O-acyltransferase 2, which is uniquely associated with CGL1 seipinopathies, with no molecular evidence for dual diagnosis.

Phenotype expansion and development in Kosaki overgrowth syndrome.

We expand the Kosaki overgrowth syndrome (KOGS) phenotype by over 70% to include 24 unreported KOGS symptoms, in a first male patient, the third overall associated with the PDGFRB c.1751C>G p.(Pro584Arg) mutation.