The HSD17B4 gene has been associated with autosomal recessive Perrault syndrome using the ClinGen Clinical Validity Framework as of 1/10/2018. This association was made using case-level data only. At least 19 missense, nonsense, frameshift variants and splice-site variants have been reported in humans. HSD17B4 was first associated with this disease in humans as early as 2010 (Pierce et al.). Association was scored in at least 7 probands in 6 publications (20673864, 23181892, 24553428, 24602372, 28830375, 27790638). Perrault syndrome is characterized by ovarian dysgenesis in females and often azoospermia in males, as well as childhood to adult onset sensorineural hearing loss and ataxia. More severe types of DBP deficiency occur which cause severe phenotypes and infant mortality. That is outside the scope of this curation, but is important to note. Very little experimental evidence exists for HSD17B4 and Perrault syndrome. In summary, HSD17B4 is definitively associated with autosomal recessive Perrault syndrome.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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