RESUMEN
Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis that is usually lethal in utero in males, though exceptionally they survive very rarely either with Klinefelter syndrome or a somatic mosaicism. We performed genomic analysis of five Japanese IP patients including a rare boy case, all of whom were definite cases with retinopathy. Four patients including the boy revealed the recurrent exon 4-10 deletion in the sole known causative gene IKBKG/NEMO, which was confirmed by various specific PCR techniques. The boy's saliva DNA showed a mosaicism consisting of the deletion and intact alleles, but his blood DNA did not. Relative quantification analysis of the real-time PCR data by ∆∆CT method estimated the mosaicism ratio of the boy's saliva as 45:55 (deletion:intact). A genomic analysis for the recurrent deletion at the nucleotide sequence level has been performed directly using patient's DNA and it has been clarified that the breakpoints are within two MER67B repeats in the intron 3 and downstream of exon 10. This is the first report of the assay for the mosaicism ratio of a male IP case with a recurrent exon 4-10 deletion of IKBKG/NEMO and the sequencing analysis of the breakpoints of the recurrent deletion directly using patient's sample.
Asunto(s)
Genómica/métodos , Quinasa I-kappa B/genética , Incontinencia Pigmentaria/patología , Mosaicismo , Enfermedades de la Retina/patología , Eliminación de Secuencia , Preescolar , Exones , Femenino , Humanos , Incontinencia Pigmentaria/complicaciones , Incontinencia Pigmentaria/genética , Lactante , Japón , Masculino , Linaje , Enfermedades de la Retina/complicaciones , Enfermedades de la Retina/genéticaRESUMEN
We analyzed two siblings in a Japanese family with delayed onset cone-rod dystrophy (CRD) using whole-exome sequencing. A novel frameshift c.1106dup (p.H370Afs*17) variant and a known missense c.2027 T > A (p.I676N) variant in CDHR1 were identified. Both patients shared the same variants, although they displayed a significant difference in disease severity. A meta-analysis of the relationship between the severity and the variant type was performed using the reported cases in the literature and did not reveal a definitive correlation.