RESUMEN
Neu-Laxova syndrome (NLS) is a lethal genetic multiple congenital anomaly syndrome of unknown prevalence representing the severe spectrum of serine biosynthesis defects associated with PHGDH, PSAT1, or PSP gene mutations. The purpose of this study was to describe clinical/molecular and pathologic features of a NLS case caused by novel heterozygous missense variant in PHGDH gene identified in his consanguineous parents.
Asunto(s)
Anomalías Múltiples/genética , Encefalopatías/genética , Anomalías Congénitas/genética , Retardo del Crecimiento Fetal/genética , Ictiosis/genética , Deformidades Congénitas de las Extremidades/genética , Microcefalia/genética , Fosfoglicerato-Deshidrogenasa/genética , Mortinato/genética , Anomalías Múltiples/mortalidad , Anomalías Múltiples/patología , Encefalopatías/mortalidad , Encefalopatías/patología , Brasil/epidemiología , Anomalías Congénitas/mortalidad , Anomalías Congénitas/patología , Consanguinidad , Femenino , Retardo del Crecimiento Fetal/mortalidad , Retardo del Crecimiento Fetal/patología , Genes Letales/genética , Predisposición Genética a la Enfermedad , Humanos , Ictiosis/mortalidad , Ictiosis/patología , Deformidades Congénitas de las Extremidades/mortalidad , Deformidades Congénitas de las Extremidades/patología , Microcefalia/mortalidad , Microcefalia/patología , Mutación Missense/genética , Embarazo , Mortinato/epidemiologíaRESUMEN
Leigh syndrome is an early onset progressive disorder caused by defects in mitochondrial oxidative phosphorylation. Pathogenic variants in nuclear and mitochondrial genes are associated with the syndrome. Homozygous pathogenic variants in the C12orf65 gene impair the mitochondrial oxidative phosphorylation system. We describe a new case of Leigh syndrome caused by a novel pathogenic variant of the C12orf65 gene resulting in the lack of the Gly-Gly-Gln (GGQ) domain in the predicted protein, and review clinical and molecular data from previously reported patients. Our study supports that the phenotype caused by C12orf65 gene variants is heterogeneous and varies from spastic paraparesis to Leigh syndrome. Loss-of-function variants are more likely to cause the disease, and variants affecting the GGQ domain tend to be associated with more severe phenotypes, reinforcing a possible genotype-phenotype correlation.