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A novel mutation in retinitis pigmentosa GTPase regulator gene with a distinctive retinitis pigmentosa phenotype in a Chinese family.

Sheng X, Li Z, Zhang X, Wang J, Ren H, Sun Y, Meng R, Rong W, Zhuang W - Mol. Vis. (2010)

Bottom Line: Mutation screening demonstrated a novel mutation ORF15+577_578 delAG, which caused an open reading frameshift and resulted in premature truncation of the RPGR protein.The mutation was detected in eight affected male individuals and 14 obligate female carriers of the family and was found to segregate with the phenotype in this family.However, the state associated with the carrier was moderate to high myopia with the refractive error ranging from -5.00 D to 22.00 D in 14 female carriers.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, People Hospital of Ningxia Hui Autonomous Region, Yinchuan, China.

ABSTRACT

Purpose: To screen the mutation in the retinitis pigmentosa GTPase regulator (RPGR) ORF15 in a large Chinese family with X-linked recessive retinitis pigmentosa and describe the phenotype in affected male and female carriers.

Methods: Ophthalmic examination was performed on 77 family members to identify affected individuals and to characterize the disease phenotype. PCR and direct sequencing were used for screening mutations in the RPGR gene.

Results: Mutation screening demonstrated a novel mutation ORF15+577_578 delAG, which caused an open reading frameshift and resulted in premature truncation of the RPGR protein. The mutation was detected in eight affected male individuals and 14 obligate female carriers of the family and was found to segregate with the phenotype in this family. The mutation led to a severe retinitis pigmentosa (RP) phenotype in male-affected individuals, with some variability in the age of onset of night blindness and visual acuity, but was recessive in female carriers without an RP phenotype. However, the state associated with the carrier was moderate to high myopia with the refractive error ranging from -5.00 D to 22.00 D in 14 female carriers.

Conclusions: This novel mutation in RPGR ORF15 causes a serious RP phenotype in males and no RP phenotype in female carriers. Moderate to high myopia was a particular feature for female carriers in this pedigree. Our finding expands the spectrum of RPGR mutations causing X-linked RP and expands phenotypic spectrum of the disease in a Chinese family. This finding will be useful for further genetic consultations and genetic diagnosis.

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Related in: MedlinePlus

Pedigree with six generations. The circles represent females, and the squares represent males; slashed symbols indicate deceased family members. The filled black symbols denote family members with retinitis pigmentosa, open symbols indicate unaffected individuals, and circles with a dot indicate female carriers. The arrow marks the index patient (proband).
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f1: Pedigree with six generations. The circles represent females, and the squares represent males; slashed symbols indicate deceased family members. The filled black symbols denote family members with retinitis pigmentosa, open symbols indicate unaffected individuals, and circles with a dot indicate female carriers. The arrow marks the index patient (proband).

Mentions: There are 82 family members in the pedigree, including five individuals who have passed away. Eight affected males were diagnosed by ophthalmic exam. A six-generation pedigree (with 41 males and 36 females still living) was compiled and revealed X-linked recessive inheritance (Figure 1). Eight affected males and 14 obligate carriers in the six-generation family were assessed.


A novel mutation in retinitis pigmentosa GTPase regulator gene with a distinctive retinitis pigmentosa phenotype in a Chinese family.

Sheng X, Li Z, Zhang X, Wang J, Ren H, Sun Y, Meng R, Rong W, Zhuang W - Mol. Vis. (2010)

Pedigree with six generations. The circles represent females, and the squares represent males; slashed symbols indicate deceased family members. The filled black symbols denote family members with retinitis pigmentosa, open symbols indicate unaffected individuals, and circles with a dot indicate female carriers. The arrow marks the index patient (proband).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927444&req=5

f1: Pedigree with six generations. The circles represent females, and the squares represent males; slashed symbols indicate deceased family members. The filled black symbols denote family members with retinitis pigmentosa, open symbols indicate unaffected individuals, and circles with a dot indicate female carriers. The arrow marks the index patient (proband).
Mentions: There are 82 family members in the pedigree, including five individuals who have passed away. Eight affected males were diagnosed by ophthalmic exam. A six-generation pedigree (with 41 males and 36 females still living) was compiled and revealed X-linked recessive inheritance (Figure 1). Eight affected males and 14 obligate carriers in the six-generation family were assessed.

Bottom Line: Mutation screening demonstrated a novel mutation ORF15+577_578 delAG, which caused an open reading frameshift and resulted in premature truncation of the RPGR protein.The mutation was detected in eight affected male individuals and 14 obligate female carriers of the family and was found to segregate with the phenotype in this family.However, the state associated with the carrier was moderate to high myopia with the refractive error ranging from -5.00 D to 22.00 D in 14 female carriers.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, People Hospital of Ningxia Hui Autonomous Region, Yinchuan, China.

ABSTRACT

Purpose: To screen the mutation in the retinitis pigmentosa GTPase regulator (RPGR) ORF15 in a large Chinese family with X-linked recessive retinitis pigmentosa and describe the phenotype in affected male and female carriers.

Methods: Ophthalmic examination was performed on 77 family members to identify affected individuals and to characterize the disease phenotype. PCR and direct sequencing were used for screening mutations in the RPGR gene.

Results: Mutation screening demonstrated a novel mutation ORF15+577_578 delAG, which caused an open reading frameshift and resulted in premature truncation of the RPGR protein. The mutation was detected in eight affected male individuals and 14 obligate female carriers of the family and was found to segregate with the phenotype in this family. The mutation led to a severe retinitis pigmentosa (RP) phenotype in male-affected individuals, with some variability in the age of onset of night blindness and visual acuity, but was recessive in female carriers without an RP phenotype. However, the state associated with the carrier was moderate to high myopia with the refractive error ranging from -5.00 D to 22.00 D in 14 female carriers.

Conclusions: This novel mutation in RPGR ORF15 causes a serious RP phenotype in males and no RP phenotype in female carriers. Moderate to high myopia was a particular feature for female carriers in this pedigree. Our finding expands the spectrum of RPGR mutations causing X-linked RP and expands phenotypic spectrum of the disease in a Chinese family. This finding will be useful for further genetic consultations and genetic diagnosis.

Show MeSH
Related in: MedlinePlus