RESUMEN
Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities, and occasional or late-onset retinal pigmentation. We ascertained eight families affected by HS and, by using a whole-exome sequencing approach, identified biallelic mutations in PEX1 or PEX6 in six of them. Loss-of-function mutations in both genes are known causes of a spectrum of autosomal-recessive peroxisome-biogenesis disorders (PBDs), including Zellweger syndrome. PBDs are characterized by leukodystrophy, hypotonia, SNHL, retinopathy, and skeletal, craniofacial, and liver abnormalities. We demonstrate that each HS-affected family has at least one hypomorphic allele that results in extremely mild peroxisomal dysfunction. Although individuals with HS share some subtle clinical features found in PBDs, the diagnosis was not suggested by routine blood and skin fibroblast analyses used to detect PBDs. In conclusion, our findings define HS as a mild PBD, expanding the pleiotropy of mutations in PEX1 and PEX6.
Asunto(s)
Adenosina Trifosfatasas/genética , Amelogénesis Imperfecta/genética , Fibroblastos/patología , Pérdida Auditiva Sensorineural/genética , Proteínas de la Membrana/genética , Mutación/genética , Uñas Malformadas/genética , Peroxisomas/patología , ATPasas Asociadas con Actividades Celulares Diversas , Adolescente , Adulto , Estudios de Casos y Controles , Células Cultivadas , Niño , Preescolar , Femenino , Fibroblastos/metabolismo , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Linaje , Peroxisomas/metabolismo , Fenotipo , Pronóstico , Tasa de Supervivencia , Adulto JovenRESUMEN
Human immunodeficiency virus (HIV) infection is a disease described as having significant and frequent oral manifestations with an early onset character. Which could be a very interesting diagnostic clue. The odonto-stomatologist is therefore in the front line to detect the immunodeficiency caused by this pathology, even though the patient may be unaware of his condition or the aggravation of it, as was the case with our patient.