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M A Ramos-Arroyo

Publications and source records attributed to M A Ramos-Arroyo.

At least 19 recordsLinked to original sources
PubMed2005

Incidence and mutation rates of Huntington's disease in Spain: experience of 9 years of direct genetic testing.

BACKGROUND: Prior to the discovery of the Huntington's disease (HD) mutation, the prevalence, incidence, and new mutation rates for this disease were based on the presence of progressive choreic movements and a positive family history. OBJECTIVE: To evaluate the uptake of the HD genetic analysis in Spain, and to provide additional information on the epidemiology of this disease from the experience of 9 years of direct genetic testing. METHODS: From 1994 to 2002, CAG repeat length was determined in 317 patients with symptoms compatible with HD. In all cases, demographic, clinical, and family data were carefully reviewed. RESULTS: HD diagnosis (CAG repeat length >/=36) was confirmed in 166 (52%) symptomatic cases. Of these, 76 (45.8%) reported a positive family history and in 21 cases (12.7%) family history was negative. New mutation events were genetically proven in three families and highly suspected in another, estimating that the minimum new mutation rate for HD in our population is >4%, with a potential mutation rate of 8%. More than 16% of all HD cases had late onset (>59 years) of symptoms, and in three quarters of these the family history was negative. The incidence rate for the autonomous communities of Navarra and the Basque country, based on the number of newly diagnosed cases by genetic testing, was 4.7 per million per year. CONCLUSIONS: Direct HD genetic testing shows that the incidence and mutation rates of the disease are 2-3 times higher than previously reported. We also demonstrated the relevance of CAG repeat length assessment in diagnosing patients with late onset of symptoms and negative family history for HD.

Adolescent↗
PubMed2001

Heat-shock protein 70-1 and HLA class II gene polymorphisms associated with celiac disease susceptibility in Navarra (Spain).

Heat shock proteins (HSP) are thought to play a role in the immune response making probable their contribution to celiac disease (CD). We studied the polymorphisms in the 5' regulatory region of the HSP70-1 gene and performed genomic HLA-DQ and -DR typing in 128 CD patients and 94 healthy controls from Navarra (Spain). The frequency of the C allele of the HSP70-1, characterized by the intermediate electrophoretic mobility of DNA, was significantly increased among CD patients (64.5% vs 37.2%. p <1 x 10(-7)). When subjects were stratified by the HLA II genotype, differences were statistically significant between DR3-negative or DR3-DQB1*02-negative CD patients and matched controls. Homozygosity for the DQB1*02 allele was present in 48.4% of CD patients and 12.8% of controls (OR = 6.4; CI:3.1 to 13.8; p <1 x 10(-7)). Similar increased risk was observed for DQB1*02/*02, DRB1*03/-, or DRB1*03/07 patients. Furthermore, those individuals expressing the classical HLA alleles in CD (DQB1*02/*02, DRB1*03/*07) who also carried the HSP70-1 CC genotype were twelve times more likely to develop the disease than the matched controls. We therefore conclude that although HSP70-1 gene does not seem to be primarily associated with CD, it might be a component of the high risk haplotype, playing a role as an additional predisposing gene for the disease.

5' Untranslated Regions↗
PubMed2000

Familial choanal atresia with maxillary hypoplasia, prognathism, and hypodontia.

We report on two sibs and a cousin with bilateral choanal atresia. At 2 months, one sib died of complications following surgical correction of her defects. We evaluated her brother and cousin at age 7 and 9 years, respectively. Both had a tall forehead, maxillary hypoplasia, prognathism, and absence of certain deciduous and permanent teeth. Psychomotor development was appropriate for age. Roentgenocephalometric analyses of several relatives showed that one grandfather of these children and two of the five uncles and aunts also had maxillary hypoplasia and/or prognathism. To our knowledge, this condition has not been described previously and may represent a newly recognized autosomal dominant condition with incomplete penetrance and variable expressivity caused by a defect of neural crest development.

Adult↗
PubMed1998

A new autosomal recessive retinitis pigmentosa locus maps on chromosome 2q31-q33.

Autosomal recessive retinitis pigmentosa (ARRP) is a genetically heterogeneous disease. To date, mutations in four members of the phototransduction cascade have been implicated in ARRP. Additionally, linkage of the disease to three loci on 1p, 1q, and 6p has been described. However, the majority of cases are still uncharacterised. We have performed linkage analysis in a large nuclear ARRP family with five affected sibs. After exclusion of several regions of the genome known to contain loci for retinal dystrophies, a genomic search for linkage to ARRP was undertaken. Positive lod scores were obtained with markers on 2q31-q33 (Zmax at theta = 0.00 of 4.03, 4.12, and 4.12 at D2S364, D2S118, and D2S389, respectively) defining an interval of about 7 cM for this new ARRP locus, between D2S148 and D2S161. Forty-four out of 47 additional ARRP families, tested with markers on 2q32, failed to show linkage, providing evidence of further genetic heterogeneity.

Adult↗
PubMed1997

Down syndrome: characterisation of a case with partial trisomy of chromosome 21 owing to a paternal balanced translocation (15;21) (q26;q22.1) by FISH.

A patient with a typical Down syndrome (DS) phenotype and a normal karyotype was studied by FISH. Using painting probes, we found that the patient had partial trisomy of chromosome 21 owing to an unbalanced translocation t(15;21) (q26; q22.1) of paternal origin. To correlate genotype with phenotype as accurately as possible, we localised the breakpoint using a contig of YACs from the long arm of chromosome 21 as probes and performed FISH. We ended up with two YACs, the most telomeric giving signal on the der (15) in addition to signal on the normal chromosome 21 and the most centromeric giving signal only on both normal chromosomes 21. From these results we could conclude that the breakpoint must be located within the region encompassing YACs 280B1 and 814C1, most likely near one end of either YAC or between them, since neither YAC814C1 nor 280B1 crossed the breakpoint (most likely between marker D21S304 and marker D21S302) onband 21q22.1. The same study was performed on the chromosomes of the father and of a sister and a brother of the patient; all three carried a balanced translocation between chromosomes 15 and 21 and had a normal phenotype. We also performed a prenatal study using FISH for the sister. The fetus was also a carrier of the balanced translocation.

Adult↗
PubMed1995

Homozygous tandem duplication within the gene encoding the beta-subunit of rod phosphodiesterase as a cause for autosomal recessive retinitis pigmentosa.

Autosomal recessive retinitis pigmentosa (ARRP) is a degenerative disease of photoreceptors in which defects in the rhodopsin and phosphodiesterase beta-subunit (PDEB) loci have been reported. To assess the involvement of PDEB in ARRP families from Spain, we screened a panel of 19 families for linkage to markers within or close to the PDEB gene. Homozygosity was also tested in cases of consanguinity. This combined approach ruled out PDEB as the cause of the disease in all but one of the families. Molecular characterization of the gene in that family (a consanguineous pedigree) revealed a homozygous 71-bp tandem duplication in exon 1 of the affected member, the parents being heterozygous. This defect causes a frameshift mutation which leads to a premature stop codon, suggesting that this mutant allele is the underlying cause of ARRP in this patient. According to the data presented here, the PDEB gene is not the main gene responsible for ARRP, but accounts for about 5% of the cases.

Base Sequence↗
PubMed1994

Further delineation of pseudotrisomy 13 syndrome: a case without polydactyly.

We report on a baby with holoprosencephaly, median cleft lip, cardiac and genital anomalies, normal upper limbs, and a 46,XX karyotype. We also reviewed 22 karyotypically normal cases whose clinical features resembled trisomy 13 syndrome and compared them with the case we present. The problem of variable expression of the pseudotrisomy 13 syndrome versus genetic heterogeneity is illustrated.

Abnormalities, Multiple↗
PubMed1992

Maternal diabetes: the risk for specific birth defects.

We studied the risk for specific birth defects among infants of mothers with gestational and chronic diabetes using data collected by the Spanish Collaborative Study of Congenital Malformations (ECEMC). For the years 1976 to 1985, we identified 10,087 infants with malformations and 9,994 control infants; 155 of the case infants and 89 of the controls were born to diabetic mothers. The crude odds ratio for any minor or major defect and insulin-treated diabetes was 5.5 (95% CI = 1.2, 24.8), and for major malformations it was 8.7 (95% CI = 1.8, 34.7). The risk for defects involving the central nervous system (CNS), skeletal system and cardiovascular system were significantly increased. Infants of non-insulin-treated diabetic mothers were 2.9 times more likely to have a major congenital birth defect (95% CI = 1.2, 7.2). The crude odds ratio for any major or minor defect and mothers with gestational diabetes requiring insulin was 1.9 (95% CI = 1.1, 3.4). Similar risk was observed for major defects (OR = 1.9, 95% CI = 1.0, 3.7). These results suggest that infants of insulin-treated diabetic mothers have an increased risk of developing malformations of the CNS, cardiovascular system and skeletal system. We also found an increased risk for specific defect categories among infants of mothers with gestational diabetes treated with insulin.

Abnormalities, Multiple↗
PubMed1991

Birth defects in twins: study in a Spanish population.

The risk for specific defects among twins compared to singletons was studied using data collected by the Spanish Collaborative Study of Congenital Malformations (ECEMC). A total of 136 twins had a major and/or minor congenital defect. The overall rate of congenital defects in twins (2.37%) did not deviate significantly from the rate in singletons (2.21%). Like-sex (LS) and male-male (MM) twin pairs had a slightly higher rate of birth defects than unlike-sex (US) and female-female (FF) pairs, respectively. Defects of the central nervous system, cardiovascular system and genitourinary system were significantly more frequent in LS twins than in singletons, with relative risks of 2.8, 2.5 and 1.6, respectively. No significantly increased risk was found among US twins. Among defects of the central nervous system, the rates of anencephaly, encephalocele and hydrocephaly were significantly higher in total and LS twins; however, no significantly increased risk for spina bifida was observed when compared to singletons. MM twins were also 1.9 times more likely to have hypospadias, but the risk among males of male-female (FM) pairs was decreased.

Congenital Abnormalities↗
PubMed1991

Weaver syndrome: a case without early overgrowth and review of the literature.

A female child with Weaver syndrome is described. She did not show the excessive growth characteristic of this syndrome until after adequate caloric intake was achieved by feeding through a gastric feeding tube. Her inadequate nutrition was a result of feeding difficulties during infancy. In addition, she had recurrent pulmonary infections, apneic spells, and severe developmental delay. She died at 16 months of sepsis, congestive heart failure, and respiratory arrest. The autopsy revealed marked atrophy of the brain and cardiac ventricular hypertrophy. Most of the brain changes were thought to be from hypoxia.

Congenital Abnormalities↗
PubMed1989

The role of mitochondrial DNA in Huntington's disease.

Huntington's disease is generally considered to be a late-onset neurodegenerative disorder, which follows a protracted course of deteriorating motor control and cognitive impairment. However, in a minority of cases, the onset of symptoms occurs early in life. A preponderance of the juvenile-onset HD victims have inherited the genetic defect from their fathers. This variation in age of onset, based on the sex of the affected parent, has suggested that maternally inherited genes may influence expression of the disorder. We describe a portion of a large Venezuelan HD pedigree in which both the mother and father of three juvenile-onset HD patients share a common maternal lineage. Scanning of mtDNA from members of this family with 43 restriction endonucleases failed to reveal any differences in the mitochondrial genotype that could account for the difference in age of onset between the affected father and his progeny. Members of a related family with an affected father but no juvenile-onset progeny also appeared to share the same mitochondrial genotype. In addition, the mitochondrial gene products from lymphoblast cell lines of these family members were analyzed on polyacrylamide gels after incubation of cells with [35S]methionine, but no detectable alterations were seen. Taken together, these data suggest that the maternally inherited mitochondrial genome does not play a crucial role in determining in age of onset in HD.

Adolescent↗
PubMed1988

Thanatophoric dysplasia: an autosomal dominant condition?

We present 13 cases of thanatophoric dysplasia collected in the Spanish Collaborative Study of Congenital Malformations from a total population of 517,970 births. The incidence (live and stillbirth) was 2.7 per 100,000 births. All cases were sporadic, and there was no evidence of parental consanguinity. Parental age was significantly higher as compared with control parents. These findings suggest the occurrence of autosomal dominant mutation, with an overall mutation rate of 1.34 X 10(-5) in our population, which is close to that observed in achondroplasia.

Adult↗
PubMed1988

Prevalence of dominant mutations in Spain: effect of changes in maternal age distribution.

We studied the birth prevalence of autosomal dominant mutations in Spain and estimated how a decrease in maternal age distribution may lead to reduction in dominant mutations. The data were collected by the Estudio Colaborativo Español de Malformaciones Congénitas from April, 1976, to December, 1985. Among 553,270 liveborn infants monitored during the period, 66 infants with autosomal dominant conditions were identified. These included Apert, Crouzon, Hay-Wells, Treacher-Collins, Robinow, Stickler, Adams-Oliver, and the blepharophimosis syndromes, achondroplasia, cleidocranial dysostosis, and thanatophoric dysplasia. The overall rate of autosomal dominant conditions was 1.2 per 10,000 liveborn infants. Thirteen (20%) had an affected relative, and 52 (79%) had a negative family history. One case was excluded because of insufficient family data. The rate of autosomal dominant mutations was 0.9 per 10,000 liveborn infants, or 47 per 1 million gametes. A reduction in the maternal age distribution of mothers age 35 years and older from the current 10.8% to 4.9%, as in Atlanta, Georgia, would reduce the rate of Down syndrome in Spain by 33% and through a change in parternal age distribution may lead to a reduction in dominant mutations of about 9.6%. This suggests that a public health campaign to reduce older maternal age distribution in Spain may also lead to a reduction in dominant mutations and emphasizes the potential that a direct campaign for fathers to complete their families before age 35 years may have a small, but measurable, effect in the primary prevention of dominant mutations.

Adult↗
PubMed1988

Twin study: relationship between birth weight, zygosity, placentation, and pathologic placental changes.

We examined the placentas of 182 like-sexed live-born twins: 73 placentas (40.1%) were monochorionic and 109 (59.9%) were dichorionic. All twin pairs with monochorionic placentas were monozygotic (MZ), but 28.9% of pairs with dichorionic placentas were MZ. Analysis of birth weights demonstrated that dichorionic and dizygotic (DZ) twins were heaviest, and suggested that the chorion status is a more important determinant of birth weight than zygosity. Vascular anastomoses were identified only in monochorionic placentas and occurred in 79.5% of cases. All placentas with deep anastomoses had superficial anastomoses. A higher proportion of velamentous and marginal insertions of the umbilical cord in monochorionic placentas (27.4%) compared to dichorionic placentas (13.8%) supports the belief that lateral placental growth is greatest in twin gestations in which the embryos are initially most closely apposed--The theory of trophotropism.

Birth Weight↗
PubMed1988

[Determining factors in the intrauterine development of twins: possible effect of gestational age, sex and type of twins].

Authors present a study on 9,862 malformed newborns and 9,950 controls collected among 481,362 births monitored by Spanish Collaborative Study of Congenital Malformations (ECEML) from March 1976 to March 1985. Newborn twins (malformed and controls) had a significantly lower birthweight and mortality rate within first three days of life than singletons. Difference in birthweight was not dependent on gestational age. On the other hand, males and females of unlike-sexed twin pairs were heavier than males and females of like-sexed pairs, respectively. Malformation rates in twins and singletons were not significantly different; among twins, the higher figure corresponded to like-sexed pairs, and more specifically, to those in which both members of the pair were males. Possible influence of gestational age, sex and type of twinning (like or unlike sex) on the process of intrauterine development in twins, is discussed.

Birth Weight↗