Igarashi T, Inatomi J, Sekine T, Takeshima Y, et al
A nonsense mutation in the Na/HCO3 cotransporter gene (SLC4A4)
in a patient with permanent isolated proximal renal tubular
acidosis and bilateral glaucoma
Am Soc Nephrol Ann Mtg -- Toronto
J Am Soc Nephrol
(Sep) 11:106A 2000
Permanent isolated proximal renal tubular acidosis (pRTA)
with ocular abnormalities is a systemic disease with short stature,
isolated pRTA and ocular abnormalities. We have reported two homozygous
inactivating missense mutations (R298S and R510S) of kidney Na+/HCO3-
cotransporter (NBC-1a) gene (SLC4A4) in two unrelated Japanese patients
with permanent isolated pRTA with glaucoma, cataract, and bandkeratopathy
(Nature Genet 23: 264-266, 1999).
This time, we screened the NBC-1a cDNA
from the peripheral lymphocyte of a patient with permanent isolated pRTA
and bilateral glaucoma and have identified homozygous mutation, C to T
transitions at nucleotide 234, resulting in the formation of stop codon at
codon 29. This homozygous mutation, Q29X, was identified in the unique 5'
end of SLC4A4 of the patient.
Cosegregation of this Q29X mutation with the
disease and heterozygosity in the affected mother and father were
identified, and the absence of this mutation in 156 alleles from 78
Japanese individuals indicated that this mutation is directly related to
the disease and it is not a common DNA sequence polymorphism.
This nonsense mutation predicts truncated NBC-1a that lacks the 1,007 amino
acids, and the effect upon NBC-1a is likely to be a loss of function. In
contrast, this mutaton predicts not to have an effect upon NBC-1b
Our results have implications for understanding the role
of NBC-1a in the pathophysiology of pRTA and ocular abnormalities such as
cataracts, glaucoma and
Copyright 2000, American Society