1. High prevalence of congenital deafness on Reunion Island is due to a founder variant of LHFPL5
- Author
-
Kheira Mezouaghi, Marie-Line Jacquemont, Julie Litzler, Natalie Loundon, Souad Gherbi, Jean-Paul Bonnefont, Ines Ben Aissa, Justine Lerat, Françoise Denoyelle, François Cartault, Françoise Darcel, Laurence Jonard, Isabelle Rouillon, Crystel Bonnet, Fabienne Saint James Digeon, Emmanuelle Génin, Agnès Guichet, Sandrine Marlin, Erea-Noel Garabedian, Roselyne Gesny, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de génétique moléculaire [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Otorhinolaryngologie [CHU Limoges], Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de génétique, Centre hospitalier Félix Guyon, Bellepierre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de neurologie, CHR Réunion, Service d'ORL pédiatrique et Chirurgie Cervico-faciale [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)
- Subjects
Male ,0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Profound deafness ,Bilateral Vestibulopathy ,[SDV]Life Sciences [q-bio] ,Motor Disorders ,Deafness ,030105 genetics & heredity ,Biology ,Compound heterozygosity ,Frameshift mutation ,Mice ,03 medical and health sciences ,Exome Sequencing ,Electroretinography ,otorhinolaryngologic diseases ,Genetics ,medicine ,Animals ,Humans ,Frameshift Mutation ,Genetics (clinical) ,Vestibular areflexia ,High prevalence ,Homozygote ,Infant ,Membrane Proteins ,Pedigree ,Indian ocean ,030104 developmental biology ,Female ,Tomography, X-Ray Computed ,Founder effect - Abstract
International audience; Reunion Island is a French oversea department in the Indian Ocean with 1.6/1000, an estimated prevalence of deafness that is almost double as compared to the mainland France. Twelve children having isolated bilateral prelingual profound deafness along with motor delay attributed to vestibular areflexia were enrolled. Their mean walking age was 19 months. Electroretinography and temporal bone CT-scans were normal in all cases. A novel homozygous frameshift lipoma HMGIC fusion partner-like 5 (LHFPL5) variant c.185delT p.(Phe62Serfs*23) was identified using whole-exome sequencing. It was found in seven families. Four patients from two different families from both Reunion Island and mainland France, were compound heterozygous: c.185delT p.(Phe62Serfs*23) and c.472C > T p.(Arg158Trp). The phenotype observed in our patients completely mimics the hurry-scurry (hscy) murine Tmhs knock-out model. The recurrent occurrence of same LHFPL5 variant in Reunion Island is attributed to common ancestor couple born in 1693.
- Published
- 2018