Biallelic variants in the ciliary gene TMEM67 cause RHYNS syndrome.
Eur J Hum Genet
; 26(9): 1266-1271, 2018 09.
Article
en En
| MEDLINE
| ID: mdl-29891882
ABSTRACT
A rare syndrome was first described in 1997 in a 17-year-old male patient presenting with Retinitis pigmentosa, HYpopituitarism, Nephronophthisis and Skeletal dysplasia (RHYNS). In the single reported familial case, two brothers were affected, arguing for X-linked or recessive mode of inheritance. Up to now, the underlying genetic basis of RHYNS syndrome remains unknown. Here we applied whole-exome sequencing in the originally described family with RHYNS to identify compound heterozygous variants in the ciliary gene TMEM67. Sanger sequencing confirmed a paternally inherited nonsense c.622A > T, p.(Arg208*) and a maternally inherited missense variant c.1289A > G, p.(Asp430Gly), which perturbs the correct splicing of exon 13. Overall, TMEM67 showed one of the widest clinical continuum observed in ciliopathies ranging from early lethality to adults with liver fibrosis. Our findings extend the spectrum of phenotypes/syndromes resulting from biallelic TMEM67 variants to now eight distinguishable clinical conditions including RHYNS syndrome.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Fenotipo
/
Retinitis Pigmentosa
/
Alelos
/
Hipopituitarismo
/
Proteínas de la Membrana
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Eur J Hum Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Italia