Perrault syndrome: Evidence for progressive nervous system involvement

Fiumara, Agata; Sorge, Giovanni; Toscano, Antonio; Parano, Enrico; Pavone, Lorenzo; Opitz, John M.

doi:10.1002/ajmg.a.20616

Cited by 44 publications

(52 citation statements)

References 12 publications

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“…In addition to SNHL and ovarian dysgenesis, they had progressive sensorimotor neuropathy, ataxia and learning difficulties [2,6]. HSD17B4 encodes D-bifunctional protein (DBP), mutations in which cause DBP deficiency (MIM261515).…”

Section: Dear Sirsmentioning

confidence: 99%

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Perrault syndrome: further evidence for genetic heterogeneity

Clayton‐Smith

Mehta

et al. 2011

J Neurol

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Section: Dear Sirsmentioning

confidence: 99%

“…The disorder was first described in 1951 and subsequently there have been several reports detailing a wide variety of additional clinical features [1]. The most commonly reported additional manifestations are neurological, including mental retardation, cerebellar ataxia, and sensorimotor neuropathy [2][3][4].…”

Section: Dear Sirsmentioning

confidence: 99%

Perrault syndrome: further evidence for genetic heterogeneity

Clayton‐Smith

Mehta

et al. 2011

J Neurol

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“…The syndrome is also genetically heterogeneous. In one family, Perrault syndrome is caused by mutations in HSD17B4, encoding 17β-hydroxysteroid dehydrogenase type 4 (9,10). In 10 other families diagnosed with Perrault syndrome, HSD17B4 sequences were wild type.…”

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confidence: 99%

Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome

Pierce

Chisholm

Lynch

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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234

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Perrault syndrome is a genetically heterogeneous recessive disorder characterized by ovarian dysgenesis and sensorineural hearing loss. In a nonconsanguineous family with five affected siblings, linkage analysis and genomic sequencing revealed the genetic basis of Perrault syndrome to be compound heterozygosity for mutations in the mitochondrial histidyl tRNA synthetase HARS2 at two highly conserved amino acids, L200V and V368L. The nucleotide substitution creating HARS2 p.L200V also created an alternate splice leading to deletion of 12 codons from the HARS2 message. Affected family members thus carried three mutant HARS2 transcripts. Aminoacylation activity of HARS2 p.V368L and HARS2 p.L200V was reduced and the deletion mutant was not stably expressed in mammalian mitochondria. In yeast, lethality of deletion of the single essential histydyl tRNA synthetase HTS1 was fully rescued by wild-type HTS1 and by HTS1 p.L198V (orthologous to HARS2 p.L200V), partially rescued by HTS1 p.V381L (orthologous to HARS2 p.V368L), and not rescued by the deletion mutant. In Caenorhabditis elegans, reduced expression by RNAi of the single essential histydyl tRNA synthetase hars-1 severely compromised fertility. Together, these data suggest that Perrault syndrome in this family was caused by reduction of HARS2 activity. These results implicate aberrations of mitochondrial translation in mammalian gonadal dysgenesis. More generally, the relationship between HARS2 and Perrault syndrome illustrates how causality may be demonstrated for extremely rare inherited mutations in essential, highly conserved genes.

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“…Fiumara et al, has reported that Perrault syndrome is classified into type I, static, without neurologic features, and type II, with progressive neurologic disease due to its heterogenous nature [7].…”

Section: Discussionmentioning

confidence: 99%

Perrault Syndrome – A Rare Case Report

Sampathkumar

Veerasigamani

2015

JCDR

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An 18-year-old female presented to the outpatient department with history of not attaining menarche. She was deaf mute since birth. She was the eldest child of the family. She was born to parents of consanguineous marriage. Her younger brother aged 16-year-old was 156 cms tall and had normal speech, hearing and age appropriate development of secondary sexual characters. Her mother was 164 cms tall and had attained menarche at 15 y. There was no history of similar complaints or any other significant medical disease in the family.On examination, she had high arched palate, her height was 146 cm, her arm span (153 cm) was more than her height with no other marfanoid features. The patient had poorly developed breasts (Tanner stage 2), sparse pubic and axillary hair (Tanner stage 2). She had normal external genitalia. Her vitals were normal. Internal Medicine SectionPerrault Syndrome -A Rare Case Report ABSTRACTPerrault syndrome is a rare disease comprising pure gonadal dysgenesis (46 XX) and sensorineural hearing loss in females and deafness alone in affected males. It is an autosomal recessive disorder. Over the years many additional features like marfanoid habitus and central nervous system findings have also been reported. Herein we report a case of sporadic Perrault syndrome in 18-year-old female who presented to our hospital with deaf mutism and primary amenorrhoea. On evaluation, the patient had hypergonadotropic hypogonadism, streak gonads and a normal karyotype (46 XX). Audiologic evaluation showed sensorineural deafness. The patient was started on hormone replacement therapy. She is on regular follow up. We present this case for its infrequent incidence and also to add to the ever expanding clinical spectrum of this disease.

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Perrault syndrome: Evidence for progressive nervous system involvement

Cited by 44 publications

References 12 publications

Perrault syndrome: further evidence for genetic heterogeneity

Perrault syndrome: further evidence for genetic heterogeneity

Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome

Perrault Syndrome – A Rare Case Report

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