Recurrent biparental hydatidiform mole: additional evidence for a 1.1-Mb locus in 19q13.4 and candidate gene analysis.
J Soc Gynecol Investig
; 12(5): 376-83, 2005 Jul.
Article
em En
| MEDLINE
| ID: mdl-15979551
ABSTRACT
OBJECTIVES:
A maternal autosomal recessive mutation causing recurrent biparentally inherited complete hydatidiform moles (BiCHM) in affected women was previously mapped to a 12.4-cM interval in 19q13.4, which was recently further narrowed to a smaller 1.1-Mb region at the centromeric end. It is believed that the mutant gene in this condition is a major contributor to the regulation of imprinting in the maternal germline. To confirm and possibly narrow the critical interval we studied additional rare familial and recurrent cases.METHODS:
Using polymorphic marker analysis, we first confirmed biparental inheritance on the studied molar tissues. We then performed targeted homozygosity mapping with markers in 19q13.4 on DNA from affected women of a new large consanguineous pedigree, an additional potentially familial case, and three cases with sporadic recurrent CHM. Direct sequencing of coding exons and Southern analysis with a coding-region probe for one candidate gene (NALP5) was also performed.RESULTS:
Biparental inheritance was confirmed for those molar tissues available for analysis. All women, except for one of the isolated cases, were homozygous for markers in the identified 1.1-Mb region in 19q13.4. No mutations or large genomic rearrangements were found in NALP5 (MATER), a gene with oocyte-specific expression. Heterozygosity for a single-nucleotide polymorphism in exon 13 of NALP5 in one patient may refine the candidate region to 1.0 Mb.CONCLUSIONS:
The reported candidate region for BiCHM in 19q13.4 was confirmed in additional families, further establishing it as the major locus that harbors a gene mutated in this condition.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Uterinas
/
Cromossomos Humanos Par 19
/
Mola Hidatiforme
Limite:
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
J Soc Gynecol Investig
Assunto da revista:
GINECOLOGIA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos