Online Mendelian Inheritance in Man (OMIM)

# 300511

PREMATURE OVARIAN FAILURE 2A; POF2A

Phenotype-Gene Relationships

TEXT

A number sign (#) is used with this entry because of evidence that premature ovarian failure-2A (POF2A) is caused by mutation in the DIAPH2 gene (300108) on chromosome Xq22. One such family has been reported.

Description

Premature ovarian failure-2A (POF2A) is a defect of ovarian development and is characterized by primary or secondary amenorrhea, with elevated levels of serum gonadotropins, or by early menopause (Bione et al., 1998).

Sala et al. (1997) and Bione et al. (1998) suggested that several genes in a region defined as POF2 (Xq13.3-q22) can influence ovary development and/or oogenesis.

For a phenotypic description and a discussion of genetic heterogeneity of premature ovarian failure, see POF1 (311360).

Clinical Features

Bione et al. (1998) reported a 17-year-old girl with POF who had secondary amenorrhea and no other associated features. Her mother was diagnosed with premature menopause at the age of 32 years. At diagnosis, both mother and daughter had high gonadotropin levels.

Inheritance

The transmission pattern of POF2A in the family reported by Bione et al. (1998) was consistent with X-linked dominant inheritance.

Mapping

Powell et al. (1994) suggested that there may be a gene on Xq other than POF1 associated with premature ovarian failure. They identified a patient with premature ovarian failure and a balanced X/autosome translocation from study of DNA probes in the chromosomally normal parents and brother of the patient and somatic cell hybrids containing each translocation chromosome. They showed that the translocation was derived from the father and was localized to the region of Xq13.3-q21.1, between PGK1 and DXS447, a distance of 0.1 cM.

Sala et al. (1997) analyzed 11 balanced X;autosome translocations associated with POF, including that of patient 'BC,' who was previously studied by Philippe et al. (1993) and Philippe et al. (1995). Sala et al. (1997) used FISH to map the translocations to a YAC contig spanning most of Xq21 and constructed between the DXS223 and DXS1171 loci. The contig corresponded to a genomic region of about 15 Mb and contained the entirety of the X-Y homologous region. The most proximal and distal breakpoints associated with POF were mapped 15 Mb apart. The remaining breakpoints were localized along this large region, in the X-specific and in the X-Y homologous region. Two breakpoints in the same or in flanking STS intervals were found in 4 of the YACs. The results confirmed cytologic findings and suggested that a minimum of 8 different genes in Xq21 may be involved in ovary development. The authors concluded that the interruption of such loci could be the cause of POF.

Molecular Genetics

In a 17-year-old girl (patient BC) with secondary amenorrhea and a balanced X;12 translocation, previously studied by Philippe et al. (1993) and Philippe et al. (1995) and in whom Sala et al. (1997) mapped the breakpoint to a specific YAC, Bione et al. (1998) demonstrated that the translocation breakpoint was in the last intron of the DIAPH2 gene (300108.0001). The proband's mother, who carried the same chromosomal rearrangement, was diagnosed with premature menopause at the age of 32 years; both had high gonadotropin levels at diagnosis. Bione et al. (1998) noted that mutant alleles of Drosophila 'diaphanous' (dia) are responsible for sterility in male and female fruit flies.

REFERENCES

Contributors:

Marla J. F. O'Neill - updated : 04/18/2017

Creation Date:

Anne M. Stumpf : 10/26/2004

Edit History:

carol : 06/24/2024
alopez : 06/21/2024
carol : 05/10/2017
carol : 04/18/2017
carol : 04/17/2017
carol : 04/05/2012
carol : 6/23/2006
alopez : 6/22/2006
alopez : 11/2/2004
alopez : 10/26/2004