Phenotype-genotype correlation in potential female carriers of X-linked developmental cataract (Nance-Horan syndrome).
OBJECTIVE
To correlate clinical examination with underlying genotype in asymptomatic females who are potential carriers of X-linked developmental cataract (Nance-Horan syndrome).


METHODS
An ophthalmologist blind to the pedigree performed comprehensive ophthalmic examination for 16 available family members (two affected and six asymptomatic females, five affected and three asymptomatic males). Facial features were also noted. Venous blood was collected for sequencing of the gene NHS.


RESULTS
All seven affected family members had congenital or infantile cataract and facial dysmorphism (long face, bulbous nose, abnormal dentition). The six asymptomatic females ranged in age from 4-35 years old. Four had posterior Y-suture centered lens opacities; these four also exhibited the facial dysmorphism of the seven affected family members. The fifth asymptomatic girl had scattered fine punctate lens opacities (not centered on the Y-suture) while the sixth had clear lenses, and neither exhibited the facial dysmorphism. A novel NHS mutation (p.Lys744AsnfsX15 [c.2232delG]) was found in the seven patients with congenital or infantile cataract. This mutation was also present in the four asymptomatic girls with Y-centered lens opacities but not in the other two asymptomatic girls or in the three asymptomatic males (who had clear lenses).


CONCLUSIONS
Lens opacities centered around the posterior Y-suture in the context of certain facial features were sensitive and specific clinical signs of carrier status for NHS mutation in asymptomatic females. Lens opacities that did not have this characteristic morphology in a suspected female carrier were not a carrier sign, even in the context of her affected family members.
Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. arif.khan@mssm.edu
Arif O
AO
Khan
Mohammed A
MA
Aldahmesh
Jawahir Y
JY
Mohamed
Fowzan S
FS
Alkuraya
D000293:Adolescent; D000328:Adult; D000368:Aged; D002386:Cataract / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007908:Lens, Crystalline / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014071:Tooth Abnormalities / Q000175:diagnosis / Q000235:genetics*; D014792:Visual Acuity / Q000502:physiology
D008565:Membrane Proteins; C488621:NHS protein, human; D009687:Nuclear Proteins