TY - JOUR
T1 - Further delineation of renal-coloboma syndrome in patients with extreme variability of phenotype and identical PAX2 mutations
AU - Schimmenti, Lisa A.
AU - Cunliffe, Heather E.
AU - McNoe, Leslie A.
AU - Ward, Teresa A.
AU - French, Michelle C.
AU - Shim, Heather H.
AU - Zhang, Yao Hua
AU - Proesmans, Willem
AU - Leys, Anita
AU - Byerly, Kyna A.
AU - Braddock, Stephen R.
AU - Masuno, Mitsuno
AU - Imaizumi, Kiyoshi
AU - Devriendt, Koen
AU - Eccles, Michael R.
PY - 1997/4
Y1 - 1997/4
N2 - Renal-coloboma syndrome is a recently described autosomal dominant syndrome of abnormal optic nerve and renal development. Two families have been reported with renal-coloboma syndrome and mutations of the PAX2 gene. The PAX2 gene, which encodes a DNA-binding protein, is expressed in the developing ear, CNS, eye, and urogenital tract. Ocular and/or renal abnormalities have been consistently noted in the five reports of patients with renal-coloboma syndrome, to date, but PAX2 expression patterns suggest that auditory and CNS abnormalities may be additional features of renal- coloboma syndrome. To determine whether additional clinical features are associated with PAX2 mutations, we have used PCR-SSCP to identify PAX2 gene mutations in patients. We report here four patients with mutations in exon 2, one of whom has severe ocular and renal disease, microcephaly, and retardation, and another who has ocular and renal disease with high-frequency hearing loss. Unexpectedly, extreme variability in clinical presentation was observed between a mother, her son, and an unrelated patient, all of whom had the same PAX2 mutation as previously described in two siblings with renal- coloboma syndrome. These results suggest that a sequence of seven Gs in PAX2 exon 2 may be particularly prone to mutation.
AB - Renal-coloboma syndrome is a recently described autosomal dominant syndrome of abnormal optic nerve and renal development. Two families have been reported with renal-coloboma syndrome and mutations of the PAX2 gene. The PAX2 gene, which encodes a DNA-binding protein, is expressed in the developing ear, CNS, eye, and urogenital tract. Ocular and/or renal abnormalities have been consistently noted in the five reports of patients with renal-coloboma syndrome, to date, but PAX2 expression patterns suggest that auditory and CNS abnormalities may be additional features of renal- coloboma syndrome. To determine whether additional clinical features are associated with PAX2 mutations, we have used PCR-SSCP to identify PAX2 gene mutations in patients. We report here four patients with mutations in exon 2, one of whom has severe ocular and renal disease, microcephaly, and retardation, and another who has ocular and renal disease with high-frequency hearing loss. Unexpectedly, extreme variability in clinical presentation was observed between a mother, her son, and an unrelated patient, all of whom had the same PAX2 mutation as previously described in two siblings with renal- coloboma syndrome. These results suggest that a sequence of seven Gs in PAX2 exon 2 may be particularly prone to mutation.
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M3 - Article
C2 - 9106533
AN - SCOPUS:16944366271
SN - 0002-9297
VL - 60
SP - 869
EP - 878
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 4
ER -