Ophthalmologic findings in Cornelia de Lange syndrome: a genotype-phenotype correlation study.
OBJECTIVE
To evaluate individuals with Cornelia de Lange syndrome previously screened for mutations in the NIPBL gene for genotype-phenotype correlations with regard to severity of ophthalmologic findings.


METHODS
Fifty-four patients with Cornelia de Lange syndrome (26 mutation positive and 28 mutation negative) with varying extent and severity of ophthalmologic findings participated in the study. We conducted a retrospective analysis of ophthalmologic data obtained through survey responses and medical records. The severity of nasolacrimal duct obstruction, myopia, ptosis, and strabismus was classified. The severity of eye findings was compared relative to the presence vs the absence of mutations in the coding region of NIPBL and relative to mutations predicted to result in a truncated protein (nonsense and frameshift mutations) vs missense mutations. Fisher exact test was used to determine the significance of these correlations.


RESULTS
A trend toward increased ptosis severity was found among individuals with truncating (nonsense and frameshift) mutations compared with individuals with missense mutations (P = .07).


CONCLUSIONS
NIPBL may be directly involved in ptosis pathogenesis.


CONCLUSIONS
Elucidating the pathogenetic mechanisms of ophthalmologic morbidities in patients with de Lange syndrome may lead to more effective treatment.
Nallasamy
Sudha
S
Division of Ophthalmology, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, USA.
Kherani
Femida
F
Yaeger
Dinah
D
McCallum
Jennifer
J
Kaur
Maninder
M
Devoto
Marcella
M
Jackson
Laird G
LG
Krantz
Ian D
ID
Young
Terri L
TL
D000293:Adolescent; D000328:Adult; D001763:Blepharoptosis / Q000235:genetics; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D003635:De Lange Syndrome / Q000235:genetics*; D005128:Eye Diseases / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D005838:Genotype; D006801:Humans; D007223:Infant; D007767:Lacrimal Duct Obstruction / Q000235:genetics; D008297:Male; D020125:Mutation, Missense; D009216:Myopia / Q000235:genetics; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D012189:Retrospective Studies; D013285:Strabismus / Q000235:genetics
D018797:Cell Cycle Proteins; D018389:Codon, Nonsense; C487465:NIPBL protein, human; D011506:Proteins