Perrault Syndrome 4

General Information (adopted from Orphanet):

Synonyms, Signs: PRLTS4
PRLTS type-4 [IBIS]
Number of Symptoms 20
OrphanetNr:
OMIM Id: 615300
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
25956234 [IBIS]
Age of onset: Childhood
Adolescent
Adult
25956234 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Perrault Syndrome
 -Rare developmental defect during embryogenesis
 -Rare endocrine disease
 -Rare genetic disease
 -Rare gynecologic or obstetric disease
 -Rare neurologic disease
 -Rare otorhinolaryngologic disease
 -Rare urogenital disease

Comment:

Perrault Syndrome 4 (PRLTS4) is a subtype / child of Perrault Syndrome. Mutations in leucyl-tRNA synthetase 2 (LARS2) gene on chromosome 3p21.31 cause PRLTS4 (OMIM 615300). LARS2 encodes a mitochondrial tRNA synthetase that appears to play a critical role of in the maintenance of ovaries and hearing (PMID:25956234)

Symptom Information: Sort by abundance 

1
 (HPO:0000786) Primary amenorrhea 26657938 IBIS 61 / 7739
2
 (HPO:0000869) Secondary amenorrhea 26657938 IBIS 42 / 7739
3
 (HPO:0000133) Gonadal dysgenesis Very frequent [IBIS] 26657938 IBIS 21 / 7739
4
 (HPO:0000876) Oligomenorrhea 26657938 IBIS 13 / 7739
5
 (HPO:0008724) Hypoplasia of the ovary 26657938 IBIS 6 / 7739
6
 (HPO:0008209) Premature ovarian failure Very frequent [IBIS] 25956234 IBIS 28 / 7739
7
 (HPO:0001587) Primary ovarian failure Very frequent [IBIS] 26970254 IBIS 9 / 7739
8
 (HPO:0000130) Abnormality of the uterus 25956234 IBIS 86 / 7739
9
 (HPO:0000013) Hypoplasia of the uterus Very frequent [IBIS] 25956234 IBIS 21 / 7739
10
 (HPO:0000813) Bicornuate uterus 26657938 IBIS 22 / 7739
11
 (HPO:0000407) Sensorineural hearing impairment Very frequent [IBIS] 25956234 IBIS 524 / 7739
12
 (HPO:0005101) High-frequency hearing impairment Very frequent [IBIS] 25956234 IBIS 16 / 7739
13
 (HPO:0001730) Progressive hearing impairment 26657938 IBIS 29 / 7739
14
 (HPO:0030338) Abnormal circulating gonadotropin level Very frequent [IBIS] 25956234 IBIS 2 / 7739
15
 (HPO:0400007) Polymenorrhea 26657938 IBIS 1 / 7739
16
 (OMIM) Increased gonadotropin levels 25956234 IBIS 3 / 7739
17
 (OMIM) Ovarian dysgenesis Very frequent [IBIS] 25956234 IBIS 7 / 7739
18
 (OMIM) Small ovaries 26657938 IBIS 4 / 7739
19
 (OMIM) Small uterus 25956234 IBIS 4 / 7739
20
 (OMIM) Upsloping audiograms 26657938 IBIS 1 / 7739

Associated genes:

LARS2;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Perrault syndrome is characterized by premature ovarian failure (POF) in females and by progressive hearing loss in both females and males (summary by Pierce et al., 2013).

For discussion of genetic heterogeneity of Perrault syndrome, see ...
Clinical Description OMIM Pierce et al. (2013) reported a consanguineous family of Palestinian ancestry in which the 17-year-old female proband presented with primary amenorrhea and postmenopausal levels of follicle-stimulating hormone and luteinizing hormone (FSH and LH; see 118850). Her uterus was ...
Molecular genetics OMIM In a consanguineous family of Palestinian ancestry with Perrault syndrome, Pierce et al. (2013) performed exome sequencing followed by filtering and identified only 1 homozygous variant, a missense mutation in the LARS2 gene (T522N; 604544.0001), that segregated with ...