This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Reprints and Permissions Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Panichkul, P. C. Articles by Van den Veyver, I. B. Search for Related Content PubMed PubMed Citation Articles by Panichkul, P. C. Articles by Al-Hussaini, T. K. Articles by Sierra, R. Articles by Kashork, C. D. Articles by Popek, E. J. Articles by Stockton, D. W. Articles by Van den Veyver, I. B. Social Bookmarking                   What's this?

Recurrent Biparental Hydatidiform Mole: Additional Evidence for a 1.1-Mb Locus in 19q13.4 and Candidate Gene Analysis

Departments of Obstetrics and Gynecology, Molecular and Human Genetics, and Pathology, Baylor College of Medicine, Houston, Texas, USA; Department of Obstetrics and Gynecology, Assiut Umnversity, Assiut, Egypt; Department of Obstetrics and Gynecology, Phramongkutklao Hospital, Bangkok, Thailand

Tarek K. Al-Hussaini, MD

Rebecca Sierra, BS

Departments of Obstetrics and Gynecology, Molecular and Human Genetics, and Pathology, Baylor College of Medicine, Houston, Texas, USA; Department of Obstetrics and Gynecology, Assiut University, Assiut, Egypt

Catherine D. Kashork, BS

Departments of Obstetrics and Gynecology, Molecular and Human Genetics, and Pathology, Baylor College of Medicine, Houston, Texas, USA; Department of Obstetrics and Gynecology, Assiut University, Assiut, Egypt; Signature Genomics Laboratonres, LLC, Spokane, Washington, USA.

Edwina J. Popek, DO

David W. Stockton, MD

Departments of Obstetrics and Gynecology, Molecular and Human Genetics, and Pathology, Baylor College of Medicine, Houston, Texas, USA; Department of Obstetrics and Gynecology, Assiut University, Assiut, Egypt

Ignatia B. Van den Veyver, MD

Departments of Obstetrics and Gynecology, Molecular and Human Genetics, and Pathology, Baylor College of Medicine, Houston, Texas, USA; Department of Obstetrics and Gynecology, Assiut University, Assiut, Egypt iveyver{at}bcm.tmc.edu

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 19q 13.4, 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 19q 13.4 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-specfic 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.

Key Words: Biparental inheritance • hydatidiform mole • maternal imprinting • 19q13.4

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?