Recurrent biparental hydatidiform mole: additional evidence for a 1.1-Mb locus in 19q13.4 and candidate gene analysis

J Soc Gynecol Investig. 2005 Jul;12(5):376-83. doi: 10.1016/j.jsgi.2005.02.011.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosome Mapping
  • Chromosomes, Human, Pair 19*
  • DNA Mutational Analysis
  • Female
  • Genetic Markers
  • Humans
  • Hydatidiform Mole / genetics*
  • Hydatidiform Mole / pathology
  • In Situ Hybridization, Fluorescence
  • Inheritance Patterns
  • Microsatellite Repeats
  • Pedigree
  • Pregnancy
  • Recurrence
  • Uterine Neoplasms / genetics*
  • Uterine Neoplasms / pathology


  • Genetic Markers