Galactose-1-phosphate uridyl transferase gene mutations in women with premature ovarian failure

Mlinar, Barbara; Geršak, Ksenija; Karas, Natasa; Žitnik, Irena Prodan; Battelino, Tadej; Lukac-Bajalo, Jana

doi:10.1016/j.fertnstert.2004.09.041

Cited by 10 publications

(6 citation statements)

References 19 publications

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“…The most common cause of classical galactosemia is the Q188R mutation, which is followed by the K285N in central European populations. A milder form of GALT deficiency is Duarte galactosemia, charac-terised by the N314D mutation and additional intron and promoter sequence variations [37].…”

Section: Follicle Dysfunctionmentioning

confidence: 99%

Premature ovarian failure from current perspective

Kökçü

2010

Gynecological Endocrinology

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Premature ovarian failure (POF) is a syndrome characterised by amenorrhoea, hypoestrogenism and hypergonadotropinism before the age of 40. It is a disorder affecting approximately 1% of women <40 years, 1/1,000 women by the age of 30 and 1/10,000 women by the age of 20. POF is not merely an early menopause. Up to 50% of the patients with POF will have intermittent and unpredictable ovarian function which may persist for some years. Heterogeneity of POF is also reflected by the variety of possible causes, including autoimmunity, toxics, drugs, radiation, infectious as well as genetic defects. HRT remains the cornerstone of treatment and the only proven method of achieving pregnancy in these patients is by ovum donation.

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Section: Follicle Dysfunctionmentioning

confidence: 99%

Premature ovarian failure from current perspective

Kökçü

2010

Gynecological Endocrinology

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“…However,that study did not take into account any infertile patients who never conceived. Nevertheless, the screening for heterogeneous GALT mutations did not yield an abnormally high frequency of these mutations among patients with known POF (Hagenfeldt et al, 1989;Kumar et al, 2005;Mlinar et al, 2005) or with infertility (Lukac .…”

Section: Ovarian Function In Heterozygous Patientsmentioning

confidence: 99%

Pathophysiology of impaired ovarian function in galactosaemia

Forges¹,

Monnier‐Barbarino²,

Leheup³

et al. 2006

Human Reproduction Update

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Classical galactosaemia is an inherited inborn error of the major galactose assimilation pathway, caused by galactose-1-phosphate uridyltransferase (GALT) deficiency. Many GALT mutations have been described, with different clinical consequences. In severe forms, newborns present with a life-threatening, acute toxic syndrome that rapidly regresses under a galactose-restricted diet. However, long-term complications, particularly cognitive and motor abnormalities, as well as hypergonadotrophic hypogonadism in female patients are still unavoidable. The pathogenesis of galactose-induced ovarian toxicity remains unclear but probably involves galactose itself and its metabolites such as galactitol and UDP-galactose. Possible mechanisms of ovarian damage include direct toxicity of galactose and metabolites, deficient galactosylation of glycoproteins and glycolipids, oxidative stress and activation of apoptosis. As there is no aetiological treatment, clinical management of ovarian failure in galactosaemic patients principally relies on hormonal replacement therapy to induce pubertal development and to prevent bone loss and other consequences of estrogen deprivation. Further investigations will be necessary to better understand the metabolic flux of galactose through its biochemical pathways and the mechanisms of these secondary complications. The aim of this article is to present an extensive review on the pathogenesis and clinical management of galactose-induced premature ovarian failure.

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“…These studies identified several heterozygous variants that are significantly more prevalent among women with POF but they are not a major cause of ovarian insufficiency (13,(23)(24)(25). Mutations in autosomal genes (galactose-1-phosphate uridylyltransferase, GALT1; transforming growth factor beta receptor, TGFBR3; inhibin alpha, INHa; forkhead box E1, FOXE1; and b-glycan) have also been related to POF (23,24,(26)(27)(28)(29)(30). Nevertheless, in most cases, the etiopathology of the disease remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Genetic investigation of four meiotic genes in women with premature ovarian failure

Mandon‐Pepin¹,

Touraine²,

Kuttenn³

et al. 2008

European Journal of Endocrinology

114

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Objective: The goal of this study was to determine whether mutations of meiotic genes, such as disrupted meiotic cDNA (DMC1), MutS homolog (MSH4), MSH5, and S. cerevisiae homolog (SPO11), were associated with premature ovarian failure (POF). Design: Case-control study. Methods: Blood sampling, karyotype, hormonal dosage, ultrasound, and ovarian biopsy were carried out on most patients. However, the main outcome measure was the sequencing of genomic DNA from peripheral blood samples of 41 women with POF and 36 fertile women (controls). Results: A single heterozygous missense mutation, substitution of a cytosine residue with thymidine in exon 2 of MSH5, was found in two Caucasian women in whom POF developed at 18 and 36 years of age. This mutation resulted in replacement of a non-polar amino acid (proline) with a polar amino acid (serine) at position 29 (P29S). Neither 36 control women nor 39 other patients with POF possessed this genetic perturbation. Another POF patient of African origin showed a homozygous nucleotide change in the tenth of DMC1 gene that led to an alteration of the amino acid composition of the protein (M200V). Conclusions: The symptoms of infertility observed in the DMC1 homozygote mutation carrier and in both patients with a heterozygous substitution in exon 2 of the MSH5 gene provide indirect evidence of the role of genes involved in meiotic recombination in the regulation of ovarian function. MSH5 and DMC1 mutations may be one explanation for POF, albeit uncommon.

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Galactose-1-phosphate uridyl transferase gene mutations in women with premature ovarian failure

Cited by 10 publications

References 19 publications

Premature ovarian failure from current perspective

Premature ovarian failure from current perspective

Pathophysiology of impaired ovarian function in galactosaemia

Genetic investigation of four meiotic genes in women with premature ovarian failure

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