First reports of fetal SMARCC1 related hydrocephalus

Nicolas Rive Le Gouard; Romain Nicolle; Mathilde Lefebvre; Antoinette Gelot; Solveig Heide; Anna Gerasimenko; Romulus Grigorescu; Nicolas Derive; Jean-Marie Jouannic; Catherine Garel; Stéphanie Valence; Geneviève Quenum-Miraillet; Sandra Chantot-Bastaraud; Boris Keren; Delphine Heron; Tania Attie-Bitach

doi:10.1016/j.ejmg.2023.104797

First reports of fetal SMARCC1 related hydrocephalus

Eur J Med Genet. 2023 Aug;66(8):104797. doi: 10.1016/j.ejmg.2023.104797. Epub 2023 Jun 5.

Authors

Nicolas Rive Le Gouard¹, Romain Nicolle², Mathilde Lefebvre³, Antoinette Gelot⁴, Solveig Heide⁵, Anna Gerasimenko⁵, Romulus Grigorescu⁴, Nicolas Derive⁶, Jean-Marie Jouannic⁷, Catherine Garel⁸, Stéphanie Valence⁹, Geneviève Quenum-Miraillet¹⁰, Sandra Chantot-Bastaraud¹⁰, Boris Keren¹¹, Delphine Heron⁵, Tania Attie-Bitach¹²

Affiliations

¹ UF de Génomique du Développement, Département de Génétique médicale, Groupe Hospitalier Pitié-Salpêtrière, AP-HP Sorbonne Université, Paris, France. Electronic address: nicolas.rive-le-gouard@aphp.fr.
² Service de Médecine Génomique des maladies rares, UF MP5, Hôpital Necker-Enfants Malades, AP-HP Université Paris Cité, Paris, France.
³ UF de Foetopathologie, CHR d'Orléans, Orléans, France.
⁴ Service de Foetopathologie, Hôpital Armand Trousseau, AP-HP Sorbonne Université, Paris, France.
⁵ UF de Génétique Médicale et CRMR « Déficience intellectuelle », Département de Génétique médicale, Groupe Hospitalier Pitié-Salpêtrière, AP-HP Sorbonne Université, Paris, France.
⁶ Laboratoire de Biologie Médicale Multisites SeqOIA, Paris, France.
⁷ Gynécologie obstétrique, Hôpital Trousseau, Centre de Référence C-MAVEM, AP-HP Sorbonne Université, Paris, France.
⁸ Service de Radiologie Pédiatrique, Hôpital Trousseau, AP-HP Sorbonne Université, Paris, France.
⁹ Service de Neurologie Pédiatrique, Hôpital Trousseau, AP-HP Sorbonne Université, Paris, France.
¹⁰ UF de Génomique Chromosomique, Département de Génétique médicale, Hôpital Armand Trousseau, AP-HP Sorbonne Université, Paris, France.
¹¹ UF de Génomique du Développement, Département de Génétique médicale, Groupe Hospitalier Pitié-Salpêtrière, AP-HP Sorbonne Université, Paris, France; Laboratoire de Biologie Médicale Multisites SeqOIA, Paris, France.
¹² Service de Médecine Génomique des maladies rares, UF MP5, Hôpital Necker-Enfants Malades, AP-HP Université Paris Cité, Paris, France; Laboratoire de Biologie Médicale Multisites SeqOIA, Paris, France. Electronic address: tania.attie@aphp.fr.

PMID: 37285932
DOI: 10.1016/j.ejmg.2023.104797

Abstract

The SMARCC1 gene has been involved in congenital ventriculomegaly with aqueduct stenosis but only a few patients have been reported so far, with no antenatal cases, and it is currently not annotated as a morbid gene in OMIM nor in the Human Phenotype Ontology. Most of the reported variants are loss of function (LoF) and are often inherited from unaffected parents. SMARCC1 encodes a subunit of the mSWI/SNF complex and affects the chromatin structure and expression of several genes. Here, we report the two first antenatal cases of SMARCC1 LoF variants detected by Whole Genome Sequencing (WGS). Ventriculomegaly is the common feature in those fetuses. Both identified variants are inherited from a healthy parent, which supports the reported incomplete penetrance of this gene. This makes the identification of this condition in WGS as well as the genetic counseling challenging.

Keywords: Aqueduct stenosis; Fetus; Incomplete penetrance; SMARCC1; Ventriculomegaly.

Publication types

Review

MeSH terms

Fetus
Genetic Counseling
Humans
Hydrocephalus* / diagnostic imaging
Hydrocephalus* / genetics
Transcription Factors / genetics

Substances

SMARCC1 protein, human
Transcription Factors