Genotype and Phenotype Heterogeneity in Perrault Syndrome

An Application of NGS for Molecular Investigations in Perrault Syndrome: Study of 14 Families and Review of the Literature

“…Premature ovarian insufficiency was characterized by primary amenorrhea in the previously described cases and in our cohort. One of our patients also presented with arachnodactyly that had been reported only once in a patient with HSD17B4 mutations [Jacob et al, ; Kim et al, ]. All family XII affected members had severe prelingual hearing impairment, as reported by Demain et al.…”

“…Recently, mutations in five different genes have been identified in PS: C10orf2 (MIM# 616138), which encodes the mitochondrial DNA helicase Twinkle; CLPP (MIM# 614129), which encodes a mitochondrial ATP‐dependent chambered protease; HARS2 (MIM# 614926), which encodes mitochondrial histidyl‐tRNA synthetase; HSD17B4 (MIM# 233400), which encodes a 17‐beta‐estradiol dehydrogenase involved in peroxisomal fatty acid beta‐oxidation; and LARS2 (MIM# 615300), which encodes mitochondrial leucyl‐tRNA synthetase [Demain et al, ]. Mutations of one of the five PS genes have been reported in 19 families for 29 females and 13 males [Pierce et al, , , ; Badura‐Stronka et al, ; Jenkinson et al, ; Kim et al, ; Morino et al, ; Ahmed et al, ; Soldà et al, ; Dursun et al., ; Demain et al, ]. However, most cases of PS are not molecularly defined [Linssen et al, ; Gottschalk et al, ; Agrawala et al, ].…”

Exome analysis identified a novel missense mutation in the CLPP gene in a consanguineous Saudi family expanding the clinical spectrum of Perrault Syndrome type-3

“…Additional clinical features including spasticity, peripheral neuropathy, ataxia, and learning difficulty have also been described [2][3][4]. SNHL and limb spasticity may start in early life with gradual progression and variable severity leading to complete deafness and wheelchair dependency or inability to walk [5,6]. The infertility features, defined by impaired sex hormone profiles and premature menopause can only be detected after puberty [2,3].…”

Primary ovarian insufficiency associated with autosomal abnormalities: from chromosome to genome-wide and beyond

“…83 HSD17B4 mutations cause Perrault syndrome, which features POI and sensorineural hearing loss. 58,59 In nonsyndromic POI, haplotype AGAAGG on HSD17B4 gene differs between POI and control group in dominant model and also has epistasis with TG gene as previously mentioned. 29 The association between steroidogenic factor 1 (SF1) and POI have been widely explored.…”