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At least 127 records · Page 7Linked to original sources
PubMed2006

Placental volume in twin and triplet pregnancies measured by three-dimensional ultrasound at 11 + 0 to 13 + 6 weeks of gestation.

OBJECTIVE: To compare the placental volume at 11 + 0 to 13 + 6 weeks' gestation between singleton and multiple pregnancies and to examine the possible effect of chorionicity on placental volume. METHODS: The placental volume was measured by three-dimensional (3D) ultrasound using the Virtual Organ Computer-aided AnaLysis (VOCAL) technique in 290 consecutive twin and 37 triplet pregnancies at 11 + 0 to 13 + 6 weeks of gestation. For the comparison of twin, triplet and singleton placental volumes each measurement was expressed as a multiple of the median (MoM) for singletons, previously established from the study of 417 normal fetuses at 11 + 0 to 13 + 6 weeks of gestation. RESULTS: Median twin and triplet placental volumes were 1.66 and 2.28 MoM for singletons, respectively. In twins the placental volumes increased significantly with gestation from a median of 83.6 mL (5th and 95th centiles: 56.0 mL and 124.9 mL) at 11 + 0 weeks to 149.3 mL (5th and 95th centiles: 100.0 mL and 223.1 mL) at 13 + 6 weeks. The median MoM in monochorionic twins was not significantly different from that in dichorionic twins with fused placentas or dichorionic twins with separate placentas. In triplets the placental volumes increased significantly with gestation from a median of 114.9 mL (5th and 95th centiles: 77.6 mL and 170.1 mL) at 11 weeks to 217.9 mL (5th and 95th centiles: 147.2 mL and 322.5 mL) at 13 + 6 weeks. There were no significant differences in total placental volume between monochorionic and dichorionic triplets, monochorionic and trichorionic triplets, or dichorionic and trichorionic triplets. CONCLUSIONS: Placental volume in multiple pregnancies does not depend on chorionicity, and the rate of placental growth between 11 and 13 + 6 weeks is not significantly different between singletons, twins and triplets. Moreover, for a given gestational age the placental volume corresponding to each fetus in twins and triplets is 83% and 76%, respectively, of the placental volume in singletons.

Adolescent↗
PubMed1993

Multifetal reduction of triplets to twins improves perinatal outcome.

OBJECTIVE: Our purpose was to compare the perinatal outcome of triplet pregnancies reduced to twins with the outcomes of continuing triplet pregnancies and twin pregnancies. STUDY DESIGN: Pregnancy outcomes of triplet pregnancies reduced to twins delivered between July 1988 and July 1992 were compared with pregnancy outcomes of continuing triplet and twin pregnancies delivered over the same time period. RESULTS: The mean gestational age at delivery for the reduced triplets was 35.6 weeks, compared with 31.2 weeks in the nonreduced triplets (p = 0.002). The perinatal mortality rate was 30 per 1000 births in the reduction group and 210 per 1000 births in the nonreduced triplets (p < 0.0001). There were no statistically significant differences between the reduced and nonreduced twins. CONCLUSION: Multifetal pregnancy reduction of triplets to twins yields an improved perinatal outcome compared with nonreduced triplets and a similar outcome compared with nonreduced twins.

Abortion, Therapeutic↗
PubMed1995

Maternal and perinatal complications in triplet compared with twin pregnancy.

OBJECTIVE: To compare maternal and perinatal complications in triplet and twin pregnancies. STUDY DESIGN: Case-controlled study in the setting of a University Hospital. Each pregnancy of a consecutive series of 40 triplet pregnancies of 20 weeks or more was matched for parity and maternal age with two sets of twins delivered in the same year. Primary end points of the analysis were maternal complications and perinatal outcome. RESULTS: Of the triplets 82% and of the twins 36% were a result of assisted reproduction. Pre-term labor occurred significantly more often in triplet than in twin gestation. Triplets had a significantly lower median birth-weight (1478 vs. 2030 g) and gestational age at delivery (32 vs. 35.5 weeks). The mean neonatal hospital stay was significantly longer in triplets, mainly related to the lower birth-weight, but there was no significant difference between triplets and twins in the incidence of major neonatal complications. CONCLUSION: This data of the anticipated perinatal outcome in triplet and twin pregnancies may be used to counsel women with a triplet pregnancy considering selective reduction to twins. All methods of assisted reproduction should aim at prevention of multifetal gestation.

Birth Weight↗
PubMed1995

Outcome of triplet pregnancies after assisted reproductive techniques: how frequent are the vanishing embryos?

OBJECTIVE: To assess the incidence of spontaneous embryo reduction as well as the obstetric and neonatal outcome of triplet gestations after assisted reproductive techniques (ART). METHODS: We analyzed the spontaneous outcome of 38 pregnancies in which three gestational sacs were identified with vaginal ultrasound between 21 and 28 days after ART. Weekly follow-up visits were scheduled during the first trimester until referral to a high-risk obstetrician. After delivery, each patient was interviewed individually and, if necessary, the obstetrician was contacted. RESULTS: The triplets delivery rate was 47.4%, whereas 31.6% delivered twins, 18.4% delivered singletons, and only one patient miscarried all three cases (2.6%). Finding three fetal heart beats was associated with a triplet delivery rate of 69.2%, a twin incidence of 19.2%, and a singleton birth rate of 11.6%. Embryo resorptions were observed mainly during the first 7 weeks of gestation and did not occur beyond the 14th week. The mean gestational age at delivery and neonatal birth weight were significantly lower among triplets (32.8 weeks and 1,740 g versus 35.3 weeks and 2,352 g in twins and 39.1 weeks and 3,122 g for singletons). Triplets had a 100% prematurity and cesarean section rate compared with 67% and 75% in twins and 0% and 43% in singletons, respectively. Hospitalization at the Neonatal Intensive Care Unit was required in 83% of newborn triplets, 29% of twins, and 0% of singletons, with a mean stay of 34 and 21 days for triplets and twins, respectively. One stillbirth and no neonatal deaths were reported, with an overall perinatal mortality rate of 11.9 per 1,000. CONCLUSIONS: Spontaneously, approximately 50% of triplet pregnancies will experience at least one embryo resorption. The ongoing triplets demand a complex and more expensive perinatal management, a strong argument to consider limiting the number of oocytes-embryos transferred in ART.

Birth Weight↗
PubMed2003

Prospective risk of fetal death in singleton, twin, and triplet gestations: implications for practice.

OBJECTIVE: To evaluate the prospective risk of fetal death in singleton, twin, and triplet pregnancies and to compare this risk with fetal and neonatal death rates. METHODS: We analyzed 11,061,599 singleton, 297,622 twin, and 15,375 triplet gestations drawn from the 1995-1998 National Center for Health Statistics linked birth and death files. Prospective risk of fetal death was expressed as a proportion of all fetuses still at risk at a given gestational age and compared with fetal death rate. Fetal death risk and neonatal death rates were represented graphically for singletons, twins, and triplets. RESULTS: The prospective risk of fetal death at 24 weeks was 0.28 per 1000, 0.92 per 1000, and 1.30 per 1000 for singletons, twins, and triplets, respectively. At 40 weeks, the corresponding risk was 0.57 per 1000 and 3.09 per 1000 for singletons and twins, respectively and, at 38 or more weeks, 13.18 per 1000 for triplets. Plots of gestation-specific prospective risk of fetal death and neonatal mortality converged for singletons and twins at term but crossed for triplets at approximately 36 weeks' gestation. CONCLUSION: Prospective risk of fetal death is greater for triplets and twins than for singletons and greater for triplets than for twins during the third trimester. The pattern corroborates with uteroplacental insufficiency as a suspected underlying mechanism. When prospective risk of fetal death exceeds neonatal mortality risk, delivery might be indicated. When this model is used, this data set suggests that it might be reasonable to consider delivery of twins by 39 weeks and triplets by 36 weeks to improve perinatal outcome.

Adult↗
PubMed2003

Neonatal outcome of triplet versus twin and singleton pregnancies: a matched case control study.

OBJECTIVE: To determine the neonatal outcome of triplet gestations versus that of singletons and twins matched for gestational age. STUDY DESIGN: All live born triplet gestations delivered between 1 April 1993 and 31 March 2000 were compared to an age matched control group consisting of live born twins and singletons. The neonatal outcome of 116 sets of triplets was compared to that of 116 sets of twins and 116 singletons. RESULTS: During a 7-year period 116 sets of triplet pregnancies were reviewed. Of 116 sets of live born triplets (348 newborns), 70.67% triplets were born between 33- and 36-week gestation, 28.44% between 28 and 32 weeks and 0.86% less than 28 weeks. Triplets were smaller in weight than singletons but not twins. Apgar score, use of prenatal steroid and sex ratio were similar in the three groups. Incidence of respiratory distress syndrome (RDS), use of surfactant, infants requiring intubation, pneumothorax, patent ductus arteriosus, sepsis, intraventricular hemorrhage, periventricular leucomalacia, retinopathy of prematurity, necrotizing enterocolitis, gastroesophageal reflux and jaundice requiring phototherapy were not statistically different among the three groups. Incidence of major and minor congenital anomalies, percent neonatal intensive care unit (NICU) admissions, and mean duration of NICU stay were also similar. There was no influence of birth order on neonatal outcome of triplet pregnancy and outcome did not significantly change over 7 years of the study period. CONCLUSIONS: Triplets have a similar outcome to twins and singletons when matched for gestational age. Since outcome is dependent on gestational age, the closer the gestational age is to term the better is the outcome.

Adult↗
PubMed2003

Perinatal mortality in triplet births in Japan: time trends and factors influencing mortality.

Perinatal mortality rates (PMRs) in triplets were analyzed using Japanese Vital Statistics during the period of 1980-1998. The total number of perinatal deaths in triplets was 1051. The PMR significantly decreased from 214 per 1000 births in 1980 to 39 in 1998, a reduction of 82%. PMRs in triplets were 11.1-fold higher in 1980 and 6.9-fold higher in 1998 than in singletons, indicating that PMRs improved more in triplets than in singletons during the last two decades in Japan. The PMR was the highest in the third-born, followed by the second- and the first-born triplets in each period. As for maternal age, the PMR was 1.5-3.7 times higher in the < 25 years of age group than the other age groups. Additionally, the PMR was the lowest for birthweight (BW) >or= 2000 g during the entire period. In addition, the PMR decreased with gestational age (GA) of up to 38-39 weeks and increased thereafter. The effects of BW on the PMR were stronger than the effects of GA. The proportion of perinatal deaths in triplets with extremely low BW (< 1000 g) was 74% in 1980-1989 and increased to 82% in 1990-1998. The declining PMR was unlikely to be due to the improvement in BW in triplets. It is likely that it was related to the improved medical management of triplets during the perinatal period and the first week of life. Information obtained in the present study may be useful in counseling pregnant woman about triplet births.

Birth Order↗
PubMed2005

Analysis of factors affecting birthweight, birth length and head circumference: study of Japanese triplets.

The aims of this study were to identify factors associated with birthweight, birth length and head circumference for triplets, and analyze these body size parameters at birth, especially head circumference, according to gestational age. The subjects of this study were 370 mothers and their 1109 triplet children (excluding one stillborn infant) who were born between 1978 and 2002. The gestational age proved to be the strongest contributing factor to birthweight, birth length and head circumference of the triplets. Moreover, sex was a significant factor affecting birthweight, birth length and head circumference. Male neonates had a higher birthweight, longer birth length and greater head circumference than female neonates. Birth order in triplets also had a significant effect on birthweight and head circumference. Lower birth-order neonates had a higher birthweight and greater head circumference. An effect of maternal pregravid body mass index (BMI) on both birthweight and birth length was observed. The birthweights of triplets born to women whose pregravid BMIs were more than 26.0 kg/m2 weighed an average of 150 g more than those of triplets born to women whose pregravid BMIs were less than 19.8 kg/m2, and the birth length of triplets born to women whose pregravid BMIs were more than 26.0 kg/m2 averaged 1.5 cm longer than those of triplets born to women whose pregravid BMIs were less than 19.8 kg/m2. Concerning head circumference, the median head circumference of male neonates was approximately 0.5 cm longer than female neonates. Compared to singleton neonates, the median head circumference of triplets was almost the same.

Birth Weight↗
PubMed2006

Perinatal and early childhood outcomes of twins versus triplets.

The purpose of this prospective cohort study of twins and triplets was to evaluate perinatal and early childhood outcomes through 18 months of age. The study population included 141 twin pregnancies (282 twin children) and 8 triplet pregnancies (24 triplet children) recruited between May, 1996 and June, 2001. Mothers of triplets versus twins were significantly more likely to have infertility treatments, to be overweight or obese before conception, to be admitted antenatally, and to deliver by cesarean section. Length of gestation for triplets was significantly shorter (-2.31 weeks, p < .0001), and more likely to be less than 35 weeks (Adjusted Odds Ratio [AOR] 9.38, 95% confidence interval [CI] 3.22-27.29). Average birthweight for triplets was significantly lighter (-495 grams, p < .0001), and more likely to be low birthweight (AOR 11.38, 95% CI 3.11-41.61). Triplets were also more likely to be admitted to neonatal intensive care (AOR 7.97, 95% CI 2.13-29.77), to require mechanical ventilation (AOR 5.67, 95% CI 2.05-15.65), to develop respiratory distress syndrome (AOR 12.50, 95% CI 3.89-40.20), or a major morbidity (retinopathy of prematurity, necrotizing enterocolitis, ventilator support, or grade III or IV intraventricular hemorrhage, AOR 5.67, 95% CI 2.05-15.65). Weight, length, and head circumference was significantly smaller at birth for triplets compared to twins, and these differences remained through 18 months of age, along with lower mental developmental scores at the oldest age. Compared to twins, triplets have greater neonatal morbidity, and through 18 months of age lower mental and motor scores, slower postnatal growth and more residual stunting, particularly of length and head circumference.

Chi-Square Distribution↗
PubMed2003

Triplets and quadruplets in Switzerland: comparison with singletons, and evolution over the last decade.

AIMS: Main objectives were 1) to determine the incidence of higher multiple births from 1995 to 1998 in Switzerland, and 2) to evaluate neonatal mortality and morbidity. Secondary objectives were 3) to compare the results with those of matched singletons, and 4) to compare the present data to the first Swiss study (1985-1988). METHODS: Retrospective analysis of maternal and neonatal data obtained from all Swiss hospitals. RESULTS: The incidence of triplet births was 1/3247 and that of quadruplet births 1/81,186. The median gestational age was 32 5/7 weeks for triplets, and 28 6/7 weeks for quadruplets. The median birth weight was 1665 g for triplets and 1076 g for quadruplets. Perinatal mortality was 6% for triplets and 19% for quadruplets. Respiratory distress syndrome was the major morbidity as diagnosed in 52% of triplets and 81% of quadruplets. A comparison of triplets with matched singletons showed no significant differences in morbidity and mortality. Compared with the first Swiss study, the mortality rate decreased, while the incidence of triplets increased but decreased for quadruplets. CONCLUSION: The incidence of higher-order multiple births in Switzerland dropped for quadruplets in the last decade but has increased for triplets. The mortality and morbidity of triplets is comparable to that of singletons with a similar gestational age.

Cesarean Section↗
PubMed2004

The ponderal index in triplets: I. Relationship to small for gestational age neonates.

The aim of the study was to examine the ponderal index in small for gestational age (SGA) triplets. Prospectively collected data from a cohort of triplets born at 28 to 37 weeks were analyzed. A low neonatal ponderal index (birth weight/[length]3) was defined as less than 1 SD below the mean (2.0), and SGA was considered as birth weight below the 10th percentile by triplet standards. We studied 2181 sets of triplets. Triplets delivered at < or = 33 weeks have a lower mean ponderal index compared with those delivered at > 33 weeks. About 70% of SGA triplets do not have a low ponderal index, whereas 79.2% of infants with a low ponderal index are not SGA by triplet standards. Both the frequency of a low ponderal index and the frequency of infants with a low ponderal index who are not SGA decrease with increasing gestational age. We conclude that the majority of triplets with a low ponderal index might not be considered growth restricted, supporting the concept that reduced fetal weight of triplets is more likely a physiological rather than a pathological phenomenon.

Anthropometry↗
PubMed1995

Ultrasonographic growth measurements in triplet pregnancies.

The incidence of triplet pregnancies is increasing due to the widespread use of ovulation induction agents and assisted conception treatments. The aim of this study was to acertain the normal ultrasonographic measurements for fetal growth parameters in triplet pregnancies. The ultrasonographic measurements of all triplet pregnancies managed in two major hospital centres were reviewed retrospectively and those in which there was less than 25% discordance in birth weight were included in the study. Triplet 50th centile for fetal biparietal diameter, whilst falling through the normal singleton centile range from 27 weeks gestation, did not fall below the 10th centile value of singletons. Triplet 50th centile for head circumference was equivalent to the singleton 10th centile from 23 weeks gestation. Triplet 50th centile for abdominal curcumference was persistently below that of the singleton 50th centile, falling below the singleton 10th centile from 29 weeks gestation. Normal growth rate of triplet gestations in the third trimester of pregnancy varies from that of singletons. An awareness of this altered growth rate is necessary to avoid the inappropriate diagnosis of asymmetrical triplet fetal growth retardation. We suggest that the growth curves presented here may be used to monitor triplet fetal growth.

Birth Weight↗
PubMedDate not supplied

[Birth weight discordance and perinatal mortality among triplets].

INTRODUCTION: The incidence of multiple births has increased in the last decade. Perinatal mortality in triplets is significantly greater than in twin and singleton births. OBJECTIVE: The objective of this study was to describe the extent of birth weight discordance among triplets and to identify its association with an increased risk of perinatal mortality. METHOD: A retrospective analysis of triplet births, for the period 1993-2003, was conducted at the Gynaecological-Obstetric Clinic "Narodni Front" in Belgrade. Birth weight discordance was defined as the difference in birth weight between the largest and the smallest triplet's weight of more than 20%. RESULTS: The rate of triplets has increased by almost 75% between the first (7.7%) and the last (29.6%) 5-year period of the last decade. Triplets are becoming more common because of the frequent use of assisted reproductive technology as a treatment for infertility. In the period 1993-2003, there were a tota of 40 triplet live births (24 weeks and greater) with incidence of 0.06%. There was no clear association between maternal age, parity, method of conception, birth gestational age, and disorders complicating pregnancy with birth discordance more than 20%. Regarding birth weight groups, statistical significance occurred only in the < 999 grams group for discordant and in the 2000-2499 grams group for concordant triplets. Overall, the perinatal mortality rate in the group was 10.8%, the foetal mortality rate was 1.7% (2/120), and the neonatal (0-28 days) mortality rate was 9.1% (11/120). An odds ratio of 95% confidence interval shows 3 times greater risk for adverse perinatal outcome in the discordant group. However, the difference was not significant. CONCLUSION: Increasing birth weight discordance may increase the risk of adverse perinatal outcome. Triplet pregnancies, being high risk, require intensive antenatal care in order to prevent preterm delivery and ultrasound in order to diagnose foetal growth abnormality and discordance, which increase foetal surveillance, through the use of biophysical profiles, non stress tests, and Doppler velocimetry, thus assessing foetal well being and the appropriate moment for obstetric intervention.

Adult↗
PubMed2003

Effect of maternal height on gestational age and birth weight in nulliparous mothers of triplets with a normal pregravid body mass index.

OBJECTIVE: To study the effect of maternal height on gestational age and birth weight of triplets born to nulliparous women with a normal pregravid body mass index (BMI). STUDY DESIGN: A 1988-2000 prospective cohort of 1,219 U.S. live-born triplets was evaluated. Patients were grouped into stature categories of 5-cm intervals. Mean values for BMI, height, maternal age, gestational age at birth, total triplet birth weight and frequencies of births at < 28 weeks and with very low birth weight were calculated for each height category. RESULTS: Maternal heights were normally distributed (mean, 165.2 +/- 6.2 cm). We found a significant positive correlation (R2 = .95), different from a zero slope (P < .01), between mean total triplet birth weight and height category. Nulliparous women who were taller than 165 cm had age, BMI and gestational age characteristics similar to those of their shorter counterparts but delivered significantly heavier triplets and were at significantly lower risk of delivering very-low-birth-weight triplets. CONCLUSION: Taller women are more likely to deliver heavier triplets and are at lower risk of delivering very-low-birth-weight triplets. This information should be included in counseling women with the potential of conceiving triplets.

Adult↗
PubMed1990

Perinatal outcome in triplet versus twin gestations.

The present study was conducted to determine whether triplet pregnancies are associated with a significantly worse perinatal outcome than twin pregnancies. Maternal and neonatal outcome was evaluated in 15 triplet and twin pregnancies that were matched for maternal age, race, type of medical insurance, delivery mode, parity, and history of previous preterm delivery. Preterm labor occurred significantly more often in triplet than in twin gestations (80 versus 40%), as did preterm delivery (87 versus 26.7%). Triplets had a significantly lower mean birth weight (1720 versus 2475 g) and gestational age at delivery (33 versus 36.6 weeks). In addition, 53.3% of triplet pregnancies but only 6.7% of twin pregnancies had one or more neonates with intrauterine growth retardation. Discordancy also occurred more frequently in triplets than in twins (66.7 versus 13.3%). The mean averaged neonatal hospital stay was significantly higher in triplets (29 versus 8.5 days), and triplets had a fivefold increased risk of requiring neonatal intensive care as compared with twins. However, there were no significant differences between the groups in maternal morbidity or major neonatal complications such as respiratory distress syndrome or intraventricular hemorrhage. We believe that these data will be useful in counseling patients with respect to the anticipated perinatal outcome of triplet pregnancies.

Adult↗
PubMed2002

Deprotonation and dimerization of maleimide in the triplet state: a laser flash photolysis study with optical and conductometric detection.

The photochemistry of maleimide in aqueous solution is governed by the coexistence of up to three different triplet states, the keto triplet (lambda(max)=250, 330 nm, lambda(min)=290 nm, pK(a)=4.4+/-0.1, tau=5 micros), the deprotonated or enolate triplet (lambda(max)=360, 260 nm, lambda(min)=320 nm, shoulder at 370-380 nm) and a dimer triplet. This biradical is formed by the addition of the keto triplet to the double bond of a ground state maleimide in competition with electron transfer, (k( (3)MI+MI)=2.6 x 10(9) dm(3) mol(-1) s(-1)). Its spectrum is identical to that of the maleimide H-adduct radical (lambda(max)=370-380 (broad), 255 nm (narrow), lambda(min)=290 nm) and its lifetime is 110 ns. While protolysis is confined to maleimide and aqueous solutions, the dimer triplet is also found in acetonitrile. Dimer triplet formation is also observed with N-ethylmaleimide. Time-resolved conductometry and buffer experiments were used to characterise excited state protolysis. Multi-wavelength "global analysis" of the time profiles allowed the separation of the transient spectra and study of the kinetics of the monomer and dimer triplets. The cyclobutane dimer yield (determined by GC) is independent of maleimide concentration. This indicates that the dimer triplet does not contribute significantly to the initiation of free-radical polymerisation. Time-dependent Hartree-Fock calculations agree with the experimental data and further confirm the proposed mechanisms.

Journal Article↗
PubMed1988

Characterization of the indole triplet excited state in proteins utilizing laser flash photolysis.

The triplet-triplet absorption spectrum of the sole indole side chain of human serum albumin and its decay kinetics were previously characterized, at room temperature, by using a conventional flash photolysis method [(1978) Proc. Natl. Acad. Sci. USA 75, 1172-1175]. Exploitation of this potentially useful long lived reporter group in protein studies was limited by the excessively large sample size required by that apparatus. The 265 nm laser flash instrument used in the present work avoids this problem at the price of a loss in photo-selectivity. We report that the latter concern can be mitigated. Melittin was studied first because this polypeptide contains a single aromatic residue (W-19), and because its monomeric and tetrameric forms are good models for solvent exposed and buried indole side chains of proteins. For both forms, the indole triplet and neutral radical absorption spectra could be readily time resolved and identified on the basis of shape and differential dioxygen sensitivity. The single tryptophan containing protein human serum albumin was studied next because it contains a large number of other 265 nm absorbing moieties whose transient spectra might complicate the detection of the indole triplet. These transients were shown to not interfere significantly in the wavelength region 450 nm to 600 nm, and, in contrast to the indole triplet, they were relatively dioxygen insensitive. Thus, a facile means is available by which the indole triplet of proteins may be characterized. Subsequently the question of whether this species could be detected in the presence of nuclei acid components was investigated by flashing the phage fd. The putative nucleic acid transients were shown not to interfere and the absorbance of the indole triplet was readily time resolved. The spectral assignment was persuasively confirmed by showing that the indole triplet absorption and phosphorescence emission spectra decay with the same lifetime. The present work thus provides additional evidence for the general applicability of the indole triplet excited state as a long lived intrinsic protein reporter group.

Bacteriophages↗
PubMed2004

Expansion of GAA triplet repeats in the human genome: unique origin of the FRDA mutation at the center of an Alu.

Friedreich ataxia is caused by expansion of a GAA triplet repeat (GAA-TR) in the FRDA gene. Normal alleles contain <30 triplets, and disease-causing expansions (66-1700 triplets) arise via hyperexpansion of premutations (30-65 triplets). To gain insight into GAA-TR instability we analyzed all triplet repeats in the human genome. We identified 988 (GAA)(8+) repeats, 291 with >or=20 triplets, including 29 potential premutations (30-62 triplets). Most other triplet repeats were restricted to <20 triplets. We estimated the expected frequency of (GAA)(6+) repeats to be negligible, further indicating that GAA-TRs have undergone significant expansion. Eighty-nine percent of (GAA)(8+) sequences map within G/A islands, and 58% map within the poly(A) tails of Alu elements. Only two other (GAA)(8+) sequences shared the central Alu location seen at the FRDA locus. One showed allelic variation, including expansions analogous to short Friedreich ataxia mutations. Our data demonstrate that GAA-TRs have expanded throughout primate evolution with the generation of potential premutation alleles at multiple loci.

Algorithms↗