Oocyte Maturation Defect 1

A number sign (#) is used with this entry because of evidence that oocyte maturation defect-1 (OOMD1) is caused by homozygous or compound heterozygous mutation in the ZP1 gene (195000) on chromosome 11q12.

Description

The zona pellucida (ZP) is a glycoprotein matrix that surrounds oocytes and has an average thickness of 17 micrometers. It is vital for the production of oocytes in early development, for fertilization, and for protection of early embryos before implantation. Absence of the zona pellucida in OOMD1 results in sterility (summary by Huang et al., 2014).

Genetic Heterogeneity of Oocyte Maturation Defects

Also see OOMD2 (616780), caused by mutation in the TUBB8 gene (616768) on chromosome 10p15; OOMD3 (617712), caused by mutation in the ZP3 gene (182889) on chromosome 7q11; OOMD4 (617743), caused by mutation in the PATL2 gene (614661) on chromosome 15q21; OOMD5 (617996), caused by mutation in the WEE2 gene (614084) on chromosome 7q34; OOMD6 (618353), caused by mutation in the ZP2 gene (182888) on chromosome 16p12; and OOMD7 (618550), caused by mutation in the PANX1 gene (608420) on chromosome 11q21.

Clinical Features

Huang et al. (2014) studied 4 sisters of Han Chinese origin, born of first-cousin parents, who were diagnosed with primary infertility and in whom assisted reproductive treatments had failed. Affected individuals had normal menstrual cycles and sex hormone levels, had no obstruction in the fallopian tubes or abnormalities of the uterus or adnexa, and were sexually active without contraception; their husbands had normal semen. Examination of oocytes from 2 of the sisters by light microscopy revealed absence of the zona pellucida (no oocytes were examined from the other 2 infertile sisters).

Zhou et al. (2019) studied 4 unrelated Chinese women, aged 28 to 33 years, with primary infertility. All 4 had normal ovarian reserves and regular menstrual cycles, and basal sex hormone levels and other infertility-related examinations did not reveal any abnormalities. However, in vitro fertilization attempts in these women resulted in retrieval of few oocytes, which all lacked a zona pellucida.

Molecular Genetics

In a consanguineous Han Chinese family in which 4 sisters were infertile and 2 had documented absence of the zona pellucida around their oocytes, Huang et al. (2014) analyzed 4 candidate genes and identified homozygosity for a frameshift mutation in the ZP1 gene (195000.0001) in the 4 affected sisters as well as an unmarried younger brother and sister. The mutation was present in heterozygosity in their fertile sister, in their mother and maternal grandmother, and in their paternal grandfather (DNA was unavailable from their deceased father).

In a 30-year-old Chinese woman (family 1) with primary infertility due to absence of the oocyte zona pellucida, Zhou et al. (2019) performed whole-exome sequencing and identified homozygosity for a missense mutation in the ZP1 gene (V570M; 195000.0002). Targeted sequencing of ZP1 in 5 more unrelated Chinese women with primary infertility due to oocyte maturation defects of the ZP revealed 3 more women with mutations in ZP1, including 1 (family 4) who was compound heterozygous for splicing mutations (195000.0003 and 195000.0004).