Perrault Syndrome 6

A number sign (#) is used with this entry because of evidence that Perrault syndrome-6 (PRLTS6) is caused by homozygous mutation in the ERAL1 gene (607435) on chromosome 17q11.

For a general phenotypic description and discussion of genetic heterogeneity of Perrault syndrome, see 233400.

Clinical Features

Chatzispyrou et al. (2017) studied 2 unrelated Dutch women from the same small village who exhibited deafness and ovarian dysgenesis, features of Perrault syndrome. The first patient was a 66-year-old-woman who had normal menarche at age 11, with irregular menses until age 27, when menopause occurred. She had been diagnosed with hearing loss at age 20 years, but hearing loss likely started much earlier and appeared to be progressive. She had a sister with sensorineural hearing loss and premature ovarian failure, who did not participate in the study. The second patient was a 38-year-old woman who was diagnosed at age 4 years with sensorineural hearing loss, which was more severe at high frequencies and was slowly progressive. At age 18, she presented with primary amenorrhea and underdeveloped secondary sexual characteristics. Abdominal ultrasound revealed streak ovaries and small uterus, and ovarian biopsy showed fibrous tissue without primordial follicles. Her father had sensorineural hearing loss from childhood, but no fertility problems; her mother and 2 sisters were healthy.

Molecular Genetics

In 2 unrelated Dutch women from the same small village with deafness and ovarian dysgenesis, Chatzispyrou et al. (2017) performed whole-exome sequencing that excluded mutations in known Perrault syndrome-associated genes and identified homozygosity for a missense mutation in the ERAL1 gene (N236I; 607435.0001) in both women. The mutation, which was not found in public variant databases, was present in heterozygosity in 49 of 530 unaffected villagers (allele frequency, 4.6%), suggesting a relatively high prevalence (0.2%) of Perrault syndrome in the village. A third woman from the village with progressive sensorineural hearing loss and primary amenorrhea presented during the course of the study and was also homozygous for N236I. In addition, the homozygous father of one of the probands exhibited sensorineural hearing loss, but had no fertility problems.