Le. Delisi et al., Investigation of a candidate gene for schizophrenia on Xq13 previously associated with mental retardation and hypothyroidism, AM J MED G, 96(3), 2000, pp. 398-403
Weak support for linkage of schizophrenia to proximal Xq has previously bee
n reported. In addition, an increased prevalence of thyroid disorder has be
en noted in families of individuals with schizophrenia, Recently, a gene ma
pped to Xq13 termed HOPA has been found to be associated with mental retard
ation, hypothyroidism, and depression and to function as a coactivator for
the thyroid receptor. We therefore examined the HOPA gene in a group of 111
probands from a larger cohort of multiplex families with schizophrenia, se
veral of whom (n = 53) also had a family history of hypothyroidism. Four ma
les and two females were found with an alteration in exon 42 of the HOPA ge
ne compared with 8/492 males and 18/471 females (942 X chromosomes) compare
d with consecutively screened newborns (chi(2) = 3.92, P < 0.05). However,
when available family members of each of the probands with an exon 42 varia
tion were subsequently screened, the mutation did not segregate with schizo
phrenia in three of five families, although all 6 probands with an exon 42
variation did have hypothyroidism in either themselves (n = 3) or their mot
hers (n = 3) (P < 0.008). These findings replicate prior findings demonstra
ting an association between HOPA polymorphisms and hypothyroidism. In addit
ion, the increased frequency of HOPA variants in this population may also p
rovide a genetic basis for the familial association of thyroid disease and
schizophrenia. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 98:398-403, 2000
. (C) 2000 Wiley-Liss, Inc.