+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Carrier detection and prenatal diagnosis in 98 families of haemophilia A by linkage analysis and direct detection of mutations



Carrier detection and prenatal diagnosis in 98 families of haemophilia A by linkage analysis and direct detection of mutations



Blood Coagulation and Fibrinolysis 2(2): 293-301



489 individuals from 98 families with a haemophilia A member were studied with restriction fragment length polymorphisms (RFLPs) for carrier detection and prenatal diagnosis. Five intragenic polymorphisms revealed with the restriction enzymes BclI, XbaI, BglI, HindIII and AlwNI and one extragenic multiallelic polymorphism (St14) at the DXS52 locus were used. The combination of the five intragenic polymorphisms did not add significantly more information than just the BclI and XbaI polymorphisms because of strong linkage disequilibrium. The sequences surrounding the intronic restriction sites of the BclI and XbaI RFLPs are known so they can be rapidly analysed using the polymerase chain reaction (PCR). 68.6% of the women were heterozygous for either the BclI or XbaI RFLP and this heterozygosity rate increased to 98.6% when the St14 extragenic polymorphism was included. Linkage analysis using these RFLPs led to the classification of over 90% of the women as carriers or normal and 98.6% of the carriers were heterozygous. Prenatal diagnosis was successful in the 16 foetuses tested and all could be classified as carrier, normal or haemophiliac. Five TaqI restriction sites in the coding region of the factor VIII gene can detect a C to T transition that results in an in-frame stop codon. These five sites were amplified by PCR in 119 haemophiliacs and tested for an abnormal TaqI restriction pattern. A stop codon was found in three haemophiliacs at exons 18, 22 and 24. The same analysis revealed three deletions, two involving the last exon 26 and one exons 23-26.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 039467538

Download citation: RISBibTeXText

PMID: 1680009

DOI: 10.1097/00001721-199104000-00012


Related references

Haemophilia A: carrier detection and prenatal diagnosis by linkage analysis using DNA polymorphism. Journal of Clinical Pathology 40(9): 971-977, 1987

Rapid carrier detection and prenatal gene diagnosis in DMD/BMD families by linkage analysis. Hunan Yi Ke Da Xue Xue Bao 27(6): 573-574, 2003

Carrier detection and prenatal diagnosis in families with haemophilia. National Medical Journal of India 14(2): 81-83, 2001

The use of DNA markers for carrier detection and prenatal diagnosis of haemophilia A in Egyptian families. Haemophilia 14(5): 1082-1087, 2008

St 14 (DX S52) VNTR polymorphism in the Indian population and its application in carrier detection and prenatal diagnosis of haemophilia A families. Haematologia 30(3): 203-207, 2000

Genomic carrier detection and prenatal diagnosis of haemophilia A in families at risk using the polymerase chain reaction (PCR). Folia Haematologica 117(4): 617-622, 1990

Inversions in the factor VIII gene: improvement of carrier detection and prenatal diagnosis in Dutch haemophilia A families. Journal of Medical Genetics 32(4): 296-300, 1995

Prevalence of the factor 8 gene intron 1 inversion in Chinese haemophiliacs and its application to carrier detection and prenatal diagnosis in haemophilia A families. Haemophilia 17(3): 541-542, 2011

Routine dna analysis of hemophilia a families for carrier detection and prenatal diagnosis. Ricerca in Clinica e in Laboratorio 16(1): 160, 1986

Carrier detection and prenatal diagnosis in haemophilia A and B. Haematologica 75(5): 424-428, 1990

Haemophilia: strategies for carrier detection and prenatal diagnosis. Bulletin of the World Health Organization 71(3-4): 429-458, 1993

Prenatal exclusion of haemophilia A and carrier testing by direct detection of a disease lesion. Prenatal Diagnosis 12(11): 861-866, 1992

Direct carrier detection for severe haemophilia A: application to families with no available affected male. Genetic Counseling 6(2): 109-112, 1995

Carrier detection and prenatal diagnosis in haemophilia in India: realities and challenges. Haemophilia 8(1): 51-55, 2002

Carrier detection and prenatal diagnosis of haemophilia. Present and future strategies. La Ricerca in Clinica E in Laboratorio 20(3): 177-185, 1990