High prevalence of congenital deafness on Reunion Island is due to a founder variant of LHFPL5

Justine Lerat (1, 2, 3) , Crystel Bonnet (4) , François Cartault , Natalie Loundon (5) , Marie‐line Jacquemont (6) , Françoise Darcel (7) , Isabelle Rouillon (8) , Kheira Mezouaghi , Agnes Guichet (9) , Julie Litzler (10) , Roselyne Gesny (11, 12) , Souad Gherbi (13) , Ines Ben Aissa , Fabienne Saint James Digeon , Eréa‐nöel Garabedian , Jean‐paul Bonnefont , Emmanuelle Genin (14) , Françoise Denoyelle (5, 12) , Laurence Jonard (1, 5) , Sandrine Marlin (8)

1 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
2 Service de génétique moléculaire [CHU Necker]
3 Otorhinolaryngologie [CHU Limoges]
4 Institut de la Vision
5 Hôpital Necker - Enfants Malades [AP-HP]
6 CHU Sainte Justine [Montréal]
7 Service de neurologie
8 CHU Trousseau [APHP]
9 Service de génétique [Angers]
10 Service de Génétique Médicale [CHU Necker]
11 Inserm U781 - Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement
12 UPD5 - Université Paris Descartes - Paris 5
13 Centre de référence des Surdités Génétiques [CHU Necker, Paris]
14 GGB - Génétique, génomique fonctionnelle et biotechnologies (UMR 1078)

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.

Domaines: Sciences du Vivant [q-bio]

Justine Lerat, Crystel Bonnet, François Cartault, Natalie Loundon, Marie‐line Jacquemont, et al.. High prevalence of congenital deafness on Reunion Island is due to a founder variant of LHFPL5. Clinical Genetics, 2018, 95 (1), pp.177-181. ⟨10.1111/cge.13460⟩. ⟨hal-03233582⟩