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Fanconi anaemia complementation group B presenting as X linked VACTERL with hydrocephalus syndrome

Fanconi anaemia complementation group B presenting as X linked VACTERL with hydrocephalus syndrome
Fanconi anaemia complementation group B presenting as X linked VACTERL with hydrocephalus syndrome
BACKGROUND: The VACTERL with hydrocephalus (VACTERL-H) phenotype is recognised to be a severe manifestation of autosomal recessive Fanconi anaemia. Several families have been described in which the VACTERL-H phenotype segregates as an X linked syndrome. The mutations which cause X linked VACTERL-H syndrome are not known.
OBJECTIVE: To determine if mutations in FANCB, which are known to cause Fanconi anaemia complementation group B, are a cause of X linked VACTERL-H syndrome.
METHODS: A three generation pedigree with X linked VACTERL-H syndrome was investigated. X inactivation was tested in carrier females, and fibroblasts from an affected male fetus were analysed for increased sensitivity to diepoxybutane. FANCB coding exons and flanking splice sites were screened for mutations by direct sequencing of polymerase chain reaction (PCR) fragments amplified from genomic DNA. cDNA from affected fetal fibroblasts was analysed by PCR and direct sequencing using specific exonic primers.
RESULTS: A FANCB mutation which results in a premature stop codon by causing skipping of exon 7 was identified. Chromosomes from the affected fetus showed increased sensitivity to diepoxybutane, and carrier women were found to have 100% skewed X inactivation in blood.
CONCLUSIONS: Mutations in FANCB are a cause of X linked VACTERL-H syndrome. The data presented are of relevance to the genetic counselling of families with isolated male cases of VACTERL-H and Fanconi anaemia
chromosomes, fanconi anemia, chromosome breakage, research, multiple, fetus, codon, dna mutational analysis, introns, London, methods, phenotype, genetics, abnormalities, rna, rna splice sites, hydrocephalus, dna, radiography, report, humans, genes, proteins, human, family, case-control studies, fetal, adult, exons, male, x-linked, fanconi anemia complementation group proteins, female, protein, fibroblasts, mutation, anemia, syndrome, research support, polymerase chain reaction, blood, pedigree
0022-2593
750-754
Holden, S.T.
31359d38-658b-4d9c-89ce-4b9146d066fa
Cox, J.J.
bd7e60bd-9378-4472-a06a-26bb84917a54
Kesterton, I.
9a6b3b36-0c6f-4d0a-a0d6-d62812734787
Thomas, N.S.
df2d7c6d-2c96-4aaa-a7ef-7f7987759cf4
Carr, C.
03985823-148f-4184-be54-1b13f2324301
Woods, C.G.
6eab4e01-70e6-4fbe-ba9c-1afa94f77f7d
Holden, S.T.
31359d38-658b-4d9c-89ce-4b9146d066fa
Cox, J.J.
bd7e60bd-9378-4472-a06a-26bb84917a54
Kesterton, I.
9a6b3b36-0c6f-4d0a-a0d6-d62812734787
Thomas, N.S.
df2d7c6d-2c96-4aaa-a7ef-7f7987759cf4
Carr, C.
03985823-148f-4184-be54-1b13f2324301
Woods, C.G.
6eab4e01-70e6-4fbe-ba9c-1afa94f77f7d

Holden, S.T., Cox, J.J., Kesterton, I., Thomas, N.S., Carr, C. and Woods, C.G. (2006) Fanconi anaemia complementation group B presenting as X linked VACTERL with hydrocephalus syndrome. Journal of Medical Genetics, 43 (9), 750-754. (doi:10.1136/jmg.2006.041673).

Record type: Article

Abstract

BACKGROUND: The VACTERL with hydrocephalus (VACTERL-H) phenotype is recognised to be a severe manifestation of autosomal recessive Fanconi anaemia. Several families have been described in which the VACTERL-H phenotype segregates as an X linked syndrome. The mutations which cause X linked VACTERL-H syndrome are not known.
OBJECTIVE: To determine if mutations in FANCB, which are known to cause Fanconi anaemia complementation group B, are a cause of X linked VACTERL-H syndrome.
METHODS: A three generation pedigree with X linked VACTERL-H syndrome was investigated. X inactivation was tested in carrier females, and fibroblasts from an affected male fetus were analysed for increased sensitivity to diepoxybutane. FANCB coding exons and flanking splice sites were screened for mutations by direct sequencing of polymerase chain reaction (PCR) fragments amplified from genomic DNA. cDNA from affected fetal fibroblasts was analysed by PCR and direct sequencing using specific exonic primers.
RESULTS: A FANCB mutation which results in a premature stop codon by causing skipping of exon 7 was identified. Chromosomes from the affected fetus showed increased sensitivity to diepoxybutane, and carrier women were found to have 100% skewed X inactivation in blood.
CONCLUSIONS: Mutations in FANCB are a cause of X linked VACTERL-H syndrome. The data presented are of relevance to the genetic counselling of families with isolated male cases of VACTERL-H and Fanconi anaemia

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More information

Published date: 2006
Keywords: chromosomes, fanconi anemia, chromosome breakage, research, multiple, fetus, codon, dna mutational analysis, introns, London, methods, phenotype, genetics, abnormalities, rna, rna splice sites, hydrocephalus, dna, radiography, report, humans, genes, proteins, human, family, case-control studies, fetal, adult, exons, male, x-linked, fanconi anemia complementation group proteins, female, protein, fibroblasts, mutation, anemia, syndrome, research support, polymerase chain reaction, blood, pedigree

Identifiers

Local EPrints ID: 59837
URI: http://eprints.soton.ac.uk/id/eprint/59837
ISSN: 0022-2593
PURE UUID: 0315ef5d-867e-43f7-ac65-4ffcf3c9c129

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Date deposited: 04 Sep 2008
Last modified: 15 Mar 2024 11:17

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Contributors

Author: S.T. Holden
Author: J.J. Cox
Author: I. Kesterton
Author: N.S. Thomas
Author: C. Carr
Author: C.G. Woods

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