Frontiers in Genetics (Jan 2024)
Recurrent “outsider” intronic variation in the SLC5A6 gene causes severe mixed axonal and demyelinating neuropathy, cyclic vomiting and optic atrophy in 3 families from Maghreb
- Lamisse Mansour-Hendili,
- Lamisse Mansour-Hendili,
- Cyril Gitiaux,
- Cyril Gitiaux,
- Madeleine Harion,
- Madeleine Harion,
- Madeleine Harion,
- Céline Latouche,
- Bénédicte Heron,
- Bénédicte Heron,
- Tanya Stojkovic,
- Mélanie Rama,
- Thomas Smol,
- Thomas Smol,
- Anne Sophie Jourdain,
- Anne Sophie Jourdain,
- Karine Mention,
- Yann Nadjar,
- Manuel Schiff,
- Manuel Schiff,
- Manuel Schiff,
- Julie Lemale,
- Jamal Ghoumid,
- Jamal Ghoumid,
- Frédéric Gottrand,
- Frédéric Gottrand,
- Cécile Talbotec,
- Agnès Rötig,
- Agnès Rötig,
- Benoît Funalot,
- Benoît Funalot,
- Isabelle Desguerre,
- Isabelle Desguerre
Affiliations
- Lamisse Mansour-Hendili
- Département de Biochimie-Biologie Moléculaire, Pharmacologie, Génétique Médicale, AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France
- Lamisse Mansour-Hendili
- IMRB Equipe Pirenne, Laboratoire d’excellence LABEX GRex, Université Paris-Est Créteil, Créteil, France
- Cyril Gitiaux
- Université Paris Cité, Paris, France
- Cyril Gitiaux
- Service de Neurophysiologie Clinique Pédiatrique, Centre de Référence des Pathologies Neuromusculaires, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France
- Madeleine Harion
- Université de Médecine, Sorbonne Université, Paris, France
- Madeleine Harion
- INSERM, Paris, France
- Madeleine Harion
- Service de Neuropédiatrie, APHP, Hôpital Trousseau, Paris, France
- Céline Latouche
- Département de Biochimie-Biologie Moléculaire, Pharmacologie, Génétique Médicale, AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France
- Bénédicte Heron
- Université de Médecine, Sorbonne Université, Paris, France
- Bénédicte Heron
- Service de Neuropédiatrie, APHP, Hôpital Trousseau, Paris, France
- Tanya Stojkovic
- Centre de Référence des maladies Neuromusculaires Nord/Est/Ile-de-France Institut de Myologie, Hôpital Pitié-Salpêtrière, Paris, France
- Mélanie Rama
- Institut de Génétique, CHU Lille, Lille, France
- Thomas Smol
- Institut de Génétique, CHU Lille, Lille, France
- Thomas Smol
- 0University of Lille, ULR7364-RADEME, Lille, France
- Anne Sophie Jourdain
- 0University of Lille, ULR7364-RADEME, Lille, France
- Anne Sophie Jourdain
- 1Service de Biochimie et Biologie Moléculaire, CHU Lille, Lille, France
- Karine Mention
- 2Centre de Référence des Maladies Héréditaires du Métabolisme, Service Néphrologie, Endocrinologie, Maladies Métaboliques et Hématologie Pédiatrique, Hôpital Jeanne de Flandre, Lille, France
- Yann Nadjar
- 3Département de Neurologie UF Neuro-Métabolisme, Centre de Référence des maladies Métaboliques et Lysosomales à expression Neurologique (CRML-Neuro), APHP-SU, Hôpital Pitié-Salpêtrière, Paris, France
- Manuel Schiff
- Université Paris Cité, Paris, France
- Manuel Schiff
- 4Reference Centre for Mitochondrial Disorders (CARAMMEL), Reference Centre for Inherited Metabolic Diseases (MaMea), Hôpital Necker-Enfants-Malades, APHP, Paris, France
- Manuel Schiff
- 5Imagine Institute, Genetics of Mitochondrial Disorders, INSERM, Paris, France
- Julie Lemale
- 6Department of Paediatric Nutrition and Gastroenterology, Reference Centre for Rare Digestive Diseases, Trousseau Hospital, APHP, Paris, France
- Jamal Ghoumid
- 0University of Lille, ULR7364-RADEME, Lille, France
- Jamal Ghoumid
- 7CHU Lille, Clinique de Génétique, Guy Fontaine, Lille, France
- Frédéric Gottrand
- 8University Lille, CHU Lille, Infinite U1286 Inserm, Lille, France
- Frédéric Gottrand
- 9Service de gastroentérologie, hépatologie et Nutrition Pédiatrique, Hôpital Jeanne de Flandre, CHU Lille, Lille, France
- Cécile Talbotec
- 0Pediatric Gastroenterology-Hepatology-Nutrition, Hôpital Necker-Enfants Malades, Paris, France
- Agnès Rötig
- Université Paris Cité, Paris, France
- Agnès Rötig
- 5Imagine Institute, Genetics of Mitochondrial Disorders, INSERM, Paris, France
- Benoît Funalot
- Département de Biochimie-Biologie Moléculaire, Pharmacologie, Génétique Médicale, AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France
- Benoît Funalot
- 1Université Paris-Est Créteil, INSERM, IMRB, Créteil, France
- Isabelle Desguerre
- Université Paris Cité, Paris, France
- Isabelle Desguerre
- 2Paediatric Neurology Department, Necker-Enfants malades University Hospital, Assistance Publique Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France
- DOI
- https://doi.org/10.3389/fgene.2024.1352006
- Journal volume & issue
-
Vol. 15
Abstract
Sodium dependent multivitamin transporter (SMVT) deficiency is a very rare autosomal recessive disorder characterized by multisystemic clinical manifestations due to combined biotin, panthotenic acid and lipoic acid deficiency. About 10 families have been described so far. Accurate diagnosis is crucial because of the possibility of a supplementation treatment with proven efficacy. Here we describe 4 new patients (3 additional families) originating from the same world region (Algeria, Maghreb). All patients, born form consanguineous parents, were homozygous carriers of the same intronic variation, outside of canonical sites, in the SLC5A6 gene encoding SMVT. RNA study in one family allowed confirming the pathogenic effect of the variation and re-classifying this variant of uncertain significance as pathogenic, opening the possibility of genetic counseling and treatment. The identification of the same variation in three distinct and apparently unrelated families is suggestive of a founder effect. The phenotype of all patients was very similar, with systematic optic atrophy (initially considered as a very rare sign), severe cyclic vomiting, and rapidly progressive mixed axonal and demyelinating sensory motor neuropathy.
Keywords
