2d-3d-human-induced-pluripotent-stem-cell-based-models-to-dissect

2D and 3D Human Induced Pluripotent Stem Cell-Based Models to Dissect Primary Cilium Involvement during Neocortical Development

Primary cilia (PC) are non-motile dynamic microtubule-based organelles that protrude from the surface of most mammalian cells. They emerge from the older ...

Université de paris

Université Paris Cité

Megacystis-microcolon-intestinal-hypoperistalsis syndrome (MMIHS) is a severe congenital visceral myopathy characterized by an abdominal distension due to a large non-obstructed urinary bladder, a microcolon and intestinal hypo- or aperistalsis. Most of the patients described to date carry a sporadic heterozygous variant in ACTG2. More recently, recessive forms have been reported and mutations in MYH11, LMOD1, MYLK and MYL9 have been described at the molecular level. In the present report, we describe five patients carrying a recurrent heterozygous variant in ACTG2. Exome sequencing performed in four families allowed us to identify the genetic cause in three. In two families, we identified variants in MMIHS causal genes, respectively a nonsense homozygous variant in MYH11 and a previously described homozygous deletion in MYL9. Finally, we identified compound heterozygous variants in a novel candidate gene, PDCL3, c.[143_144del];[380G>A], p.[(Tyr48Ter)];[(Cys127Tyr)]. After cDNA analysis, a complete absence of PDLC3 expression was observed in affected individuals, indicating that both mutated transcripts were unstable and prone to mediated mRNA decay. PDCL3 encodes a protein involved in the folding of actin, a key step in thin filament formation. Presumably, loss-of-function of this protein affects the contractility of smooth muscle tissues, making PDCL3 an excellent candidate gene for autosomal recessive forms of MMIHS.

Fetal megacystis-microcolon: Genetic mutational spectrum and identification of PDCL3 as a novel candidate gene.

We report two fetal cases carrying a de novo MID1 mutation and presenting with severe hydrothorax, suggesting the expansion of the phenotype of Opitz GBBB syndrome.

Hydrothorax in fetal cases of Opitz G/BBB diagnosis: Extending the phenotype?

Novel CDK10 variants with multicystic dysplastic kidney, left ventricular non-compaction, and a solitary median maxillary central incisor.

Neuronal ceroid lipofuscinoses (NCLs) form a clinically and genetically heterogeneous group of inherited neurodegenerative disorders that share common neuropathological features. Although they are the first cause of neurodegenerative disorders in children, their congenital forms are rarely documented. They are classically due to mutations in the CTSD gene (the CLN10 disease). Affected newborns usually present severe microcephaly, seizures and respiratory failure leading to death within the first postnatal days or weeks.

Article	Year
Fetal megacystis-microcolon: Genetic mutational spectrum and identification of PDCL3 as a novel candidate gene. Clinical genetics\| PubMed ID: 32621347	2020
Hydrothorax in fetal cases of Opitz G/BBB diagnosis: Extending the phenotype? Clinical genetics\| PubMed ID: 32926417	2020
Novel CDK10 variants with multicystic dysplastic kidney, left ventricular non-compaction, and a solitary median maxillary central incisor. Clinical genetics\| PubMed ID: 34114225	2021
Prenatal-onset of congenital neuronal ceroid lipofuscinosis with a novel CTSD mutation. Birth defects research\| PubMed ID: 34491000	2021

Lucile Boutaud

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