Three Novel Mutations in the X-Linked Juvenile Retinoschisis <i>(XLRS1)</i> Gene in 6 Japanese Patients, 1 of Whom Had Turner’s Syndrome

Abstract

We examined the XLRS1 gene for mutations in 6 Japanese patients with X-linked juvenile retinoschisis from a total of three families (5 males and 1 female), and from 3 obligate carrier females. DNA was amplified for all six coding exons of the XLRS1 gene with established primer pairs, and was sequenced directly. Each family had a different mutation, Trp96stop, 522+1g→a, and Lys167Asn in the XLRS1 gene. Affected patients had a hemizygous mutant allele while the obligate carrier females were heterozygotes who had both wild-type and mutant-type alleles. A proband female, who was the offspring of asymptomatic and nonconsanguineous parents, was found to have a chromosomal karyotype (45, X) that was indicative of Turner’s syndrome. These three different mutations in the XLRS1 gene have not been previously reported. Further studies are needed to determine the relationship between these defects in the XLRS1 gene and the phenotypic expression of the disease.

Wide-Field Imaging of Nonexudative and Exudative Congenital X-Linked Retinoschisis

“…5 However, females with overt CXLRS manifestations have been described. [26][27][28] X chromosome inactivation 29 and/or homozygosity 27,28 are implicated. Most recently, Gliem et al 30 reported an RS1 homozygous female with macular atrophy and paracentral ring of autofluorescence suggestive of a cone/cone-rod dystrophy.…”

X‐linked retinoschisis in a female with a heterozygous RS1 missense mutation

“…The mutational basis of the disease in that family has not been determined. There is also a report of XLRS in a female with Turner Syndrome [Sato et al, 2003].…”

Case report of an atypical early onset X-linked retinoschisis in monozygotic twins

“…XLRS is usually characterized by a high degree of phenotypic variability, even within the same family [ 2 ]. The three XLRS male patients of the same family with RS1 variant c.288G > A (p.Trp96Ter), previously reported in literature [ 11 ] showed peri-foveal radial micro-cysts and a silver-grey reflex in the peripheral retina. None of them presented peripheral retino-schisis.…”

“…This mutation is a stop mutation, leading to a truncated polypeptide. It is located in the discoidin domain of the protein, a crucial region for its functional activity; for these reasons it is likely pathogenic and moreover this mutation has already been associated with the disease [ 11 ]. XLRS is usually characterized by a high degree of phenotypic variability, even within the same family [ 2 ].…”