11 research outputs found
Primary open angle glaucoma due to T377M MYOC: Population mapping of a Greek founder mutation in Northwestern Greece
BACKGROUND: Mutations in the MYOC gene have been shown to explain 5% of unrelated primary open angle glaucoma (POAG) in different populations. In particular, the T377M MYOC mutation has arisen at least three separate times in history, in Great Britain, India, and Greece. The purpose of this study is to investigate the distribution of the mutation among different population groups in the northwestern region of Greece. MATERIALS AND METHODS: We explored the distribution of the "Greek" T377M founder mutation in the Epirus region in Northwestern Greece, which could be its origin. Genotyping was performed in POAG cases and controls by PCR amplification of the MYOC gene, followed by digestion with restriction enzyme. Statistical analyses were performed by an exact test, the Kaplan-Meier method and the t-test. RESULTS: In the isolated Chrysovitsa village in the Pindus Mountains, a large POAG family demonstrated the T377M mutation in 20 of 66 family members while no controls from the Epirus region (n = 124) carried this mutation (P < 0.001). Among other POAG cases from Epirus, 2 out of 14 familial cases and 1 out of 80 sporadic cases showed the mutation (P = 0.057). The probability of POAG diagnosis with advancing age among mutation carriers was 23% at age 40, and reached 100% at age 75. POAG patients with the T377M mutation were diagnosed at a mean age of 51 years (SD +/- 13.9), which is younger than the sporadic or familial POAG cases: 63.1 (SD +/- 11) and 66.8 (SD +/- 9.8) years, respectively. CONCLUSIONS: The T377M mutation was found in high proportion in members of the Chrysovitsa family (30.3%), in lower proportion in familial POAG cases (14.2%) and seems rare in sporadic POAG cases (1.2%), while no controls (0%) from the Epirus region carried the mutation. Historical and geographical data may explain the distribution of this mutation within Greece and worldwide
Melatonin and immunomodulation: Connections and potential clinical applications
Melatonin is the main hormone secreted by the pineal gland in the human
brain. It has a strong impact on the sleep- wake cycle and is considered
a general modulator of the human circadian rhythm. Apart from these
well- established properties, melatonin possesses immunomodulatory,
antioxidative and antiinflammatory properties. The potential ability of
this hormone to act synergistically with several cytokines by enhancing
their antitumoral activity and dramatically decreasing their adverse
effects has placed melatonin among the new and promising agents in
cancer immunotherapy. The use of the neurohormone alone or in
combination with cytokines and traditional chemotherapeutic drugs is
currently under vigorous investigation. Experimental and clinical trials
have already depicted some of the immunomodulatory and antitumor effects
of melatonin, delineating the need for further research in this field.
Copyright (c) 2006 S. Karger AG, Basel
Investigating the impact of the Down syndrome related common MTHFR 677C > T polymorphism in the Danish population
Chromosomal aneuploidy consists the leading cause of fetal death in our
species. Around 50% of spontaneous abortions until 15 weeks of
gestational age are chromosomally aneuploid, with trisomies accounting
for 50% of the abnormal abortions. Trisomy 21 is the most common
chromosome abnormality in liveborns and is usually the result of
nondisjunction of chromosome 21 in meiosis in either oogenesis or
spermatogenesis. To investigate the relationship between folate
metabolism and Down syndrome (DS) in a Danish population, we analyzed
the common 677C>T genetic polymorphism in the methylenetetrahydrofolate
reductase (MTHFR) gene. Our cohort consisted of 181 mothers of children
with DS versus 1,084 healthy controls. Polymerase chain reaction (PCR)
and restriction fragment length polymorphism (RFLP) were used to examine
the MTHFR 677C>T polymorphism. No significant association between the
polymorphism and the risk for DS was found. We conclude that the common
MTHFR 677C>T polymorphism is not likely to be a maternal risk factor for
DS in our cohort and that the difference to previous studies can
probably be explained by small sample size or geographic variation in
gene polymorphisms involving gene-nutritional or gene-gene or
gene-nutritional-environmental factors
Easy, Rapid, and Cost-Effective Methods for Identifying Carriers of Recurrent GJB2 Mutations Causing Nonsyndromic Hearing Impairment in the Greek Population
A variety of techniques have been developed for screening the GJB2 gene
for known and unknown mutations, especially the most common mutation in
the Caucasian population, the c. 35delG. Other mutations that have been
so far characterized in the GJB2 gene seem to have different
geographical distributions, and therefore there is an interest in
identifying recurrent mutations specific for each population and
developing easy and rapid screening techniques. Here we present easy
screening protocols for already identified recurrent mutations in the
Greek population. Developing easy, rapid, and cost-effective screening
methods will facilitate the detection of GJB2 recurrent mutation
carriers, at large, in the Greek population
Hypothesizing an Ancient Greek Origin of the GJB2 35delG Mutation: Can Science Meet History?
One specific mutation of the GJB2 gene that encodes the connexin 26
protein, the 35delG mutation, has become a major interest among
scientists who focus on the genetics of nonsyndromic hearing loss. The
mutation accounts for the majority of GJB2 mutations detected in
Caucasian populations and represents one of the most frequent disease
mutations identified so far. The debate was so far between the arguments
whether or not the 35delG mutation constitutes a mutational hot-spot or
a founder effect; however, it was recently clarified that the latter
seems the most likely. In an attempt to explore the origin and
propagation of the 35delG mutation, several groups have reported the
prevalence of the mutation and the carrier rates in different
populations worldwide. It is now certain that the theory of a common
founder prevails and that the highest carrier frequencies of the 35delG
mutation are observed in southern European populations, giving rise to a
discussion regarding the origin of the 35delG mutation. In this study,
we discuss data previously published by our and other groups and also
compare the haplotype distribution of the mutation in southern Europe,
trying to understand the pathways of science and history and the
conflict between them
Are GJB2 mutations an aggravating factor in the phenotypic expression of mitochondrial non-syndromic deafness?
Hearing impairment is a frequent condition, and genes have an important
role in its etiology. The majority of hearing loss occurs in
non-syndromic form, with deafness being the only clinically recognizable
feature. More than 60 nuclear genes or loci have been shown to be
involved in non-syndromic hearing loss, but mutations in mitochondrial
DNA also cause hearing impairment. Mitochondrial DNA mutations usually
lead to progressive hearing loss with an age of onset varying from
childhood to early adulthood. It is interesting to note that there is a
great variability among phenotypes between individuals harboring the
same mitochondrial mutation, even within the same family, and the
phenotype may range from profound deafness to completely normal hearing.
In the past years, the debate on mitochondrial mutations has been about
the penetrance, the tissue specificity and the mechanisms of modifier
genes that can modulate the severity of the phenotypic expression of the
deafness-associated mitochondrial DNA mutations. Here we summarize
evidence regarding modifying genes, and we discuss the effect of the
coexistence of mitochondrial and GJB2 mutations in families reported to
date. Journal of Human Genetics (2010) 55, 265-269;
doi:10.1038/jhg.2010.23; published online 19 March 201
Screening for Congenital Hypothyroidism: The Significance of Threshold Limit in False-Negative Results
Context: In our neonatal program, a number of infants with congenital
hypothyroidism (CH) had escaped diagnosis, when a spot RIA-TSH value of
20 mU/liter whole blood was used as a cutoff point.
Objective: The objective of the study was to find out prospectively the
additional number of newborns with CH if the TSH cutoff point is lowered
to 10 mU/liter.
Population and Methods: The study included 311,390 screened newborns.
The children with CH were followed up for a period of 3 yr.
Results: Twenty-eight percent of infants diagnosed with CH had neonatal
TSH values between 10 and 20 mU/liter (56 of 200). Forty of 47 infants,
who were reevaluated later on (85.1%), suffered permanent CH. A thyroid
scintiscan and/or echogram revealed that eight of 40 children (20.0%)
had a structural defect, and the remaining (32 of 40) had a functional
defect of the thyroid gland without anatomical abnormality; 14 of 32
cases were familial. Eighteen of the 47 reevaluated infants were
prematurely born (38.3%) and 15 of these 18 had permanent CH (83.3%).
The lowering of TSH cutoff point from 20 to 10 mU/liter resulted in a
10-fold increase of recall rate.
Conclusions: A significant number of cases with permanent CH are missed
when a TSH threshold of 20 mU/liter is applied. Almost 40% of the
missed CH cases were premature. A mild increase of TSH at screening is
not a predictor of transient CH. The increase in recall rate constitutes
a serious drawback and should be balanced against the possible
consequences of thyroid dysfunction at this important developmental
stage. (J Clin Endocrinol Metab 95: 4283-4290, 2010
The A1555G mitochondrial DNA mutation in Greek patients with non-syndromic, sensorineural hearing loss
Mitochondrial DNA mutations are undoubtedly a factor that contributes to
sensorineural, non-syndromic deafness. One specific mutation, the
A1555G, is associated with both aminoglycoside-induced and nonsyndromic
hearing impairment. The mutation is considered to be the most common of
all mitochondrial DNA deafness-causing mutations but its frequency
varies between different Populations. Here we report on the first large
screening of the A1555G mitochondrial DNA mutation in the Greek
population. The aim of this study was to determine the frequency of the
A1555G mutation in Greek sensorineural, non-syndromic deafness patients,
with childhood onset. We screened 478 unrelated Greek patients with
hearing loss of any degree and found two individuals harboring the
A1555G mutation (0.42%). Both cases had been subjected to
aminoglycosides. They were prelingual, familial and homoplasmic for the
A1555G mutation. One of the Cases Was also found heterozygous for the
frequent GJB2 35delG mutation, while the other case was negative, The
A1555G mutation seems to be less common than in other European
populations. (C) 2009 Elsevier Inc. All rights reserved
Pathologic, radiographic and molecular findings in three fetuses diagnosed with HEM/Greenberg skeletal dysplasia
BACKGROUND: Greenberg skeletal dysplasia is a very rare, autosomal recessive, in utero, lethal chondrodystrophy for which only eight index cases of diverse ethnic origin have been reported so far. The defect is associated with a defect in cholesterol biosynthesis and due to mutations in the gene encoding the lamin B receptor (LBR). METHODS: A familial case of three fetuses of a consanguineous Greek couple is presented including prenatal, physical, radiographic, histopathologic, and molecular genetic findings. RESULTS: The tentative diagnosis of Greenberg skeletal dysplasia based on pathological findings was confirmed by the identification of a homozygous, N547D amino acid substitution in the LBR gene in the third affected fetus. CONCLUSION: The present case represents the ninth described case of Greenberg dysplasia and the second case of Greek origin. The characteristic 'moth-eaten' radiographic appearance is already seen at 13 weeks' gestational ag
Low vitamin D status in preschool children in Greece
Vitamin D status in humans depends on the amount of sun exposure and
vitamin D intake. Recent reports suggest that hypovitammosis D (as
defined by serum 25-hydroxyvitamin D [25(OH)D] < 10 ng/mL) is
reemerging in developed countries and in the Middle East, pointing out
the significance of dietary and cultural practices. In the line of
prevention, we determined vitamin D status in 393 healthy preschool
children randomly selected from 7 day care centers in the Municipality
of Athens in October. The data for the analysis were collected from a
questionnaire regarding their actual dietary practices, voluntary sun
exposure, and lifestyle conditions; clinical investigation for the
determination of the skin phototype; and blood sampling for the
determination of serum 25(OH)D, parathyroid hormone, and osteocalcin
levels. Of the 393 children, 49 were immigrants. According to our
results, 6.6% of our population had serum 25(OH)D less than 10 ng/mL.
Multilinear analysis showed that the amount of sun exposure and vitamin
D intake were the direct determinants of vitamin D status. Immigrant
children presented lower serum 25(OH)D levels associated with lower
vitamin D intake and lower socioeconomic class when compared with the
Greek children. No relationship was found between 25(OH)D concentration
and skin phototype, whereas 93.3% of children used topical sunscreen.
We suggest that abundant sunlight exposure in Athens is not sufficient
to prevent hypovitarminosis D in preschool children. The extensive use
of topical sunscreens and environmental factors such as air pollution
would account for inadequate sunlight exposure and the need for dietary
intake of vitamin D. (c) 2006 Elsevier Inc. All rights reserved