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Results for “Consanguinity”

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At least 343 records · Page 19Linked to original sources

PubMed2005

Exclusion of LCA5 locus in a consanguineous Turkish family with macular coloboma-type LCA.

BACKGROUND: Leber's congenital amaurosis (LCA) is an inherited retinal dystrophy, which causes severe visual impairment in early childhood. Recent molecular genetic studies have linked 11 loci (AIPL1, CRB1, CRX, GUCY2D, RPE65, RDH12, RPGRIP1, TULP1, LCA3, LCA5, and LCA9) to LCA. LCA5 is a new locus, which maps to the 6q11-q16 chromosomal region and was found to be associated with macular coloboma-type LCA in a Pakistani family. Herein, we describe the molecular genetic features of a consanguineous Turkish family in which four children have macular coloboma-type LCA. METHODS: Haplotype analysis was performed on the DNA of the family members using microsatellite markers against GUCY2D, RPE65, and LCA5. Genomic DNA was screened for mutations by means of single-strand conformational polymorphism (SSCP) analysis in exons of the RPE65 and CRX genes. RESULTS: In haplotype analysis, no linkage to LCA5 or GUCY2D loci was detected. None of the tested markers showed homozygosity or segregation between affected siblings. PCR-SSCP mutation analysis revealed no mutations in the screened RPE65 and CRX genes. CONCLUSION: We excluded LCA5 as the genetic cause of macular coloboma-type LCA in this Turkish family. Macular coloboma-type LCA shows genetic heterogeneity and it is not possible to establish a phenotype-genotype correlation with LCA5 and macular coloboma.

Adolescent↗

PubMed1999

Variable pathogenicity of exon 43del (FAA) in four Fanconi anaemia patients within a consanguineous family.

Four Fanconi anaemia group A (FAA) patients within two related consanguineous families are presented: the propositus (male, 13 years, transplanted at age 10), and his three cousins (one male, 8 years, and two female newborns). Assignment of the patients to FAA was based on the functional complementation analysis by somatic cell hybridization and confirmed by mutation screening showing a homozygous deletion of exon 43 (4267-4404del) in the FAA gene to be present in all four patients. The newborn patients had been diagnosed prenatally by DNA analysis. In spite of identical molecular pathology and close familial relationship the clinical phenotypes of the four patients were not concordant. Discordant symptoms included birthweight, pigmentation abnormalities, skeletal, renal and genital abnormalities, whereas microcephaly and possibly the haematological course were concordant. Differences in environmental conditions and/or genetic make-up along with chance effects during development may explain discordant phenotypes despite identical molecular pathology in these patients. However, our results do not rule out the possibility that the exon 43del mutation may have prognostic value for the haematological course of the disease.

Adolescent↗

PubMed1997

Prenatal diagnosis of pseudothalidomide syndrome in consecutive pregnancies of a consanguineous couple.

Pseudothalidomide syndrome is a rare autosomal recessive condition characterized by tetraphocomelia, craniofacial abnormalities and postnatal growth restriction. We report the prenatal sonographic findings of pseudothalidomide syndrome in three consecutive pregnancies of a consanguineous couple. In the last pregnancy, the correct diagnosis was made sonographically at 11 weeks of pregnancy. The combination of transabdominal and transvaginal ultrasound examinations revealed a large cystic hygroma extending over the lower back. The lower extremities were markedly shortened with no identifiable bones below the level of the femora. The humeri on both sides were shortened; ulnae were small with no identifiable radii. The pregnancy was terminated by dilatation and curettage and diagnosis confirmed at 12 weeks of pregnancy. In conclusion, fetuses with pseudothalidomide syndrome may exhibit characteristic findings in the first trimester of pregnancy which can be detected using ultrasound.

Abnormalities, Multiple↗

PubMed1997

The comparative role of consanguinity in infant and childhood mortality in Pakistan.

As part of the 1990/1991 Pakistan Demographic and Health Survey, data were collected on the outcome of 26,408 births to 6,611 women, with mortality rates investigated at specific age intervals during the first 5 years of life. Bivariate and multivariate logistic regression analyses were employed to examine the comparative roles of consanguineous marriage and a number of demographic and socioeconomic factors, including the sex of the child, maternal age, maternal education, birth interval and birth order, as determinants of early death. The results indicate that, even after controlling for these non-genetic variables, inbreeding at the level of first cousin exerted a significant adverse effect on survival in four of the five age intervals examined, neonatal, post-neonatal, infant and under 5 years.

Child, Preschool↗

PubMedDate not supplied

[Neonatal form of a nonketotic hyperglycinemia in consanguinous parents].

This is a report of the neonatal form of nonketotic hyperglycinemia with rapid progressing neurological symptoms, respiratory distress and seizures. The EEG pattern is characteristic, the ratio of cerebrospinal fluid to plasma glycine abnormally high. The result of cranial computerized tomography demonstrates also in our patient that nonketotic hyperglycinemia joins a growing list of inborn errors of metabolism associated with brain malformations. The consanguinity of parents supports the known autosomal recessive form of inheritance.

Amino Acid Metabolism, Inborn Errors↗

PubMed1994

Bloom syndrome: an analysis of consanguineous families assigns the locus mutated to chromosome band 15q26.1.

By the principle of identity by descent, parental consanguinity in individuals with rare recessively transmitted disorders dictates homozygosity not just at the mutated disease-associated locus but also at sequences that flank that locus closely. In 25 of 26 individuals with Bloom syndrome examined whose parents were related, a polymorphic tetranucleotide repeat in an intron of the protooncogene FES was homozygous, far more often than expected (P < 0.0001 by chi 2). Therefore, BLM, the gene that when mutated gives rise to Bloom syndrome, is tightly linked to FES, a gene whose chromosome position is known to be 15q26.1. This successful approach to the assignment of the Bloom syndrome locus to one short segment of the human genome simultaneously (i) demonstrates the power of homozygosity mapping and (ii) becomes the first step in a "reverse" genetics definition of the primary defect in Bloom syndrome.

Alleles↗

PubMed2002

A novel mutation disrupting the cytoplasmic domain of CRB1 in a large consanguineous family of Palestinian origin affected with Leber congenital amaurosis.

Leber congenital amaurosis (LCA) is a genetically heterogeneous autosomal recessive condition responsible for congenital blindness or greatly impaired vision since birth. Eight LCA loci have been mapped, but only six out of eight genes have been hitherto identified. A genome-wide screen for homozygosity was conducted in a large consanguineous family originating from Palestine, for which no mutation was found in any of the six known LCA genes and that excluded the LCA3 and LCA5 loci. Evidence for homozygosity, however, was found in all affected patients of the family on chromosome 1q31, a region in which the human homologue of the Drosophila melanogaster crumbs gene (CRB1) has been mapped. Consequently, we proposed a hypothesis that the disease-causing mutation in this family might lie in an unexplored region of this LCA gene. As a matter of fact, while no mutation was found in any of the 11 CRB1 exons originally reported, we identified a 10-bp (del 4121-4130) deletion segregating with the disease in a later reported 12th exon lying in the 3' end of the gene. Interestingly, this deletion disrupts an amino acid sequence that was shown to be crucial for the function of the protein in the Drosophila counterpart (CRB).

Amino Acid Sequence↗

PubMedDate not supplied

Consanguinity and genetic morbidity in a British primary care setting: a pilot study with trained linkworkers.

OBJECTIVES: To assess the feasibility of detecting consanguineous relationships and significant genetic morbidity through screening pedigrees administered by a primary care trained linkworker. SUBJECTS AND METHODS: A case-controlled crossover study with pedigree recording by both genetic nurse specialists and a primary care worker. From 1012 records of British Pakistani patients registered with an inner city practice, 14 women, identified as having increased genetic risk, were recruited (Group 1). A further 14 age- and parity-matched women, with no indication of genetic morbidity in their General Practice records (Group 2), were also recruited. RESULTS: Valuable genetic information, not recorded in General Practice records, were ascertained through the screening pedigrees, in four members of Group 1 (29%) and six members of Group 2 (43%). There was poor agreement between the coefficients of inbreeding recorded from pedigrees prepared by the primary care worker and genetic nurse specialists (Kappa = 0.157; 95% CI 0.028-0.286). CONCLUSION: Pedigrees can be utilized as a General Practice screening tool to detect relevant genetic morbidity, not ascertained in General Practice records. The process is enhanced when a primary care worker, from the same culture as the volunteers, collects information using the patients' mother tongue.

Adult↗

PubMedDate not supplied

Strategies for the prevention of hereditary diseases in a highly consanguineous population.

Autosomal recessive hereditary diseases are relatively common in the Saudi population. The consanguinity rate is in excess of 50% and is a practice that remains strongly embedded within Saudi culture. The impact of this practice is recognized and is being addressed. Early detection and treatment of diseases can reduce mortality and minimize morbidity. This is the basis of successful neonatal screening for inborn errors of metabolism where treatment or modification of lifestyle can modulate disease. Ultimately, understanding the genetics of these diseases will provide opportunities for prevention. Options such as prenatal screening can be used to reduce the incidence of live births with inherited diseases. However, prenatal diagnosis and associated intervention is unacceptable to wide sections of all societies. Carrier detection and genetic counselling programmes have been very successful in reducing the incidence of inherited disorders in many populations. These programmes are most successful when they are sensitive to the cultural backgrounds of populations in which they are applied. In Saudi society, premarital screening to identify carrier status and the provision of appropriate counselling has tremendous potential to prevent inherited disease.

Consanguinity↗

PubMedDate not supplied

Cohorts, overlapping generations and consanguinity estimates.

A number of problems in human population genetics involve determining the effects of non-random mating due to cultural or geographic factors, and therefore requires determination of expectations based on random mating. These expectations are usually taken to be the arithmetic mean of the contributions of all possible pairs drawn from a subpopulation of individuals of mating age during a specified period. This cohort approach in effect treats the subpopulation as a discrete generation. In real populations, however, the pool of potential mates with whom any individual may be paired is continually changing, and not all pairs are eligible, on demographic grounds, to mate for equal lengths of time. A simple means of avoiding problems due to this discrepancy between method and reality is suggested and applied to data from an isolated Caribbean population in order to determine whether treating cohorts as discrete generations introduces serious bias into estimates of expected consanguinity. The results suggest that any such biases are likely to be negligible, but may be important in some special circumstances.

Adult↗

PubMedDate not supplied

A recent survey of consanguineous marriages in Japan: religion and socioeconomic class effects.

A survey of consanguineous marriages in Japan was conducted on 1 September 1983 through questionnaires. The total number of couples studied was 9225, chosen from six widely different areas of Japan. Among six religious groups, the mean inbreeding coefficient (F) is the highest in Buddhists (0.0019), and lowest in 'no religion' (0.0008) and Catholics (0.0009). The F values for Buddhists and individuals with no religion decreased with marriage year in Fukue City and in the five other areas. In the latter group, the F value for Shintoists also decreased with marriage year. In the five areas, the F value is higher in Buddhists than in the 'no religion' group in each marriage year. Among educational groups, the F value was highest in graduates of junior high school for husbands (0.0025) and wives (0.0024), whereas the F value was lowest in graduates of a college, university or graduate course for husbands (0.0006) and wives (0.0005). Occupationally, the F value was the highest in agriculture, forestry and fishery for husbands (0.0035) and wives (0.0032), whereas the rate was the lowest among salesmen, for husbands (0.0006), and in professional occupations and researchers, for wives (0.0004). The causes of the declining F value are discussed.

Consanguinity↗

PubMedDate not supplied

Consanguineous marriages and marriage payment: a study among three south Indian caste groups.

The present study aims at understanding the interrelations between consanguineous marriages and marriage payment. The data are collected from three castes inhabiting two regions of Nellore district, Andhra Pradesh, South India. It is evident from the study that the dowry system is more prevalent among higher castes, while the bride wealth system is more common among the lower castes in the hierarchy. Further, it can be seen that the dowry system is more prevalent in developed regions, while bride-wealth is more common in backward regions. Marriage payment is found to be less common in close kin marriages than in unrelated marriages. Most of the uncle-niece marriages are without any marriage payment, in all the castes. However, most of the matrilateral cross-cousin and patrilateral cross-cousin marriages are also without any marriage payment in the Devanga.

Consanguinity↗

PubMed2023

Structural and functional insights into a novel homozygous missense pathogenic variant in CUL7 identified in consanguineous Pakistani family.

3M syndrome is a rare genetic familial disorder characterized by short stature, growth retardation, facial dysmorphism, skeletal abnormalities, fleshy protruding heels, and normal intelligence, caused by mutations in the CUL7, OBSL1 and CCDC8 genes. In the present study, a novel homozygous missense variant of CUL7 (NP_001161842.1, c.4493T > C, p.L1498P) has been identified in a consanguineous Pakistani family by whole exome sequencing. In silico structural evaluation, molecular docking and simulation studies of mutant CUL7 provides substantial evidence about its crucial role in the progression of discussed ailment. The newly discovered variant significantly altered the protein's three dimensional structure, leading to abnormal interaction with binding proteins. This computational and experimental investigation provides useful information to drug developers for the synthesis of novel therapeutics against the discussed ailment.Communicated by Ramaswamy H. Sarma.

Humans↗

PubMed1999

Congenital hypothyroidism, seasonality and consanguinity in the West Midlands, England.

Seasonal variation in the incidence of congenital hypothyroidism (CHT) is reported by some centres. Also, the incidence of CHT varies with ethnic origin. We report our experience in the West Midlands, England. The overall incidence of CHT among 1128 632 neonates screened over 16 years in the West Midlands was 1:2924 live births, but was increased (1:2323; p<0.05) between October and December. In the city of Birmingham between 1981 and 1991, the incidence of CHT was 1:781, 1:5540 and 1:2257 in Pakistani, Indian and North-West European children, respectively; no cases were seen in those from other ethnic groups. Consanguinity among those of Pakistani descent could account for the increased incidence within this population. Identification of the cause of seasonal variation may aid development of preventative strategies.

Catchment Area, Health↗

PubMed2004

Homozygous WNT3 mutation causes tetra-amelia in a large consanguineous family.

Tetra-amelia is a rare human genetic disorder characterized by complete absence of all four limbs and other anomalies. We studied a consanguineous family with four affected fetuses displaying autosomal recessive tetra-amelia and craniofacial and urogenital defects. By homozygosity mapping, the disease locus was assigned to chromosome 17q21, with a maximum multipoint LOD score of 2.9 at markers D17S931, D17S1785, D17SS1827, and D17S1868. Further fine mapping defined a critical interval of approximately 8.9 Mb between D17S1299 and D17S797. We identified a homozygous nonsense mutation (Q83X) in the WNT3 gene in affected fetuses of the family. WNT3, a human homologue of the Drosophila wingless gene, encodes a member of the WNT family known to play key roles in embryonic development. The Q83X mutation truncates WNT3 at its amino terminus, suggesting that loss of function is the most likely cause of the disorder. Our findings contrast with the observation of early lethality in mice homozygous for null alleles of Wnt3. To our knowledge, this is the first report of a mutation in a WNT gene associated with a Mendelian disorder. The identification of a WNT3 mutation in tetra-amelia indicates that WNT3 is required at the earliest stages of human limb formation and for craniofacial and urogenital development.

Animals↗

PubMed1995

Consanguineous nuclear families used to identify a new locus for recessive non-syndromic hearing loss on 14q.

Hearing impairment is inherited most frequently as an autosomal recessive isolated clinical finding (non-syndromic hearing loss, NSHL). Extreme heterogeneity and phenotypic variability in the audiometric profile preclude pooling of affected families and severely hamper gene mapping by conventional linkage analysis. However, in instances of consanguinity, homozygosity mapping can be used to identify disease loci in small nuclear families. This report demonstrates the power of this technique by identifying a locus for recessive NSHL on 14q (DFNB4).

Chromosome Mapping↗

PubMed1996

Autosomal recessive non-syndromic deafness locus (DFNB8) maps on chromosome 21q22 in a large consanguineous kindred from Pakistan.

Autosomal recessive childhood-onset non-syndromic deafness is one of the most frequent forms of inherited hearing impairment. Recently five different chromosomal regions, 7q31, 11q13.5, 13q12, 14q and the pericentromeric region of chromosome 17, have been shown to harbour disease loci for this type of neurosensory deafness. We have studied a large family from Pakistan, containing several consanguineous marriages and segregating for a recessive non-syndromic childhood-onset deafness. Linkage analysis mapped the disease locus (DFNB8) on the distal long arm of chromosome 21, most likely between D21S212 and D21S1225 with the highest lod score of 7.31 at theta = 0.00 for D21S1575 on 21q22.3.

Adolescent↗

PubMed1998

Multicentre approaches to donor insemination in the French CECOS Federation: nationwide evaluation, donor matching, screening for genetic diseases and consanguinity. Centre d'Etudes et de Conservation des Oeufs et du Sperme humain.

The French CECOS Federation collates the results of its 22 sperm banks and provides annual reports on their activity. These records allow studies on many different aspects; annual nationwide evaluation, matching of donors and recipients, follow-up of pregnancies, research into artificial procreation, and natural fertility. Risk of transmitted hereditary disease is minimised by genetic screening which establishes the genealogy of donor candidates and includes karyotyping and other biological investigations when a particular risk is suspected. The real risk of consanguinity is very small. Limiting the number of children born from a given sperm donor can be defined at the local level.

Consanguinity↗