PRLTS4
MCID: PRR021
MIFTS: 29

Perrault Syndrome 4 (PRLTS4)

Categories: Ear diseases, Endocrine diseases, Fetal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Perrault Syndrome 4

MalaCards integrated aliases for Perrault Syndrome 4:

Name: Perrault Syndrome 4 57 73 29 6 71
Prlts4 57 73
Perrault Syndrome, Type 4 39

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive


HPO:

31
perrault syndrome 4:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Perrault Syndrome 4

OMIM® : 57 Perrault syndrome-4 (PRLTS4) is an autosomal recessive disorder primarily characterized by early-onset sensorineural hearing loss in both males and females, and premature ovarian failure (POF) in females. Affected individuals may also develop neurologic involvement, including developmental delay or learning difficulties in childhood or onset of progressive movement abnormalities, such as spasticity, in adulthood. Brain imaging may show progressive leukodystrophy (summary by Pierce et al., 2013, Kosaki et al., 2018 and van der Knaap et al., 2019). For a discussion of genetic heterogeneity of Perrault syndrome, see PRLTS1 (233400). (615300) (Updated 05-Mar-2021)

MalaCards based summary : Perrault Syndrome 4, also known as prlts4, is related to perrault syndrome and perrault syndrome 1. An important gene associated with Perrault Syndrome 4 is LARS2 (Leucyl-TRNA Synthetase 2, Mitochondrial). Affiliated tissues include uterus and ovary, and related phenotypes are cognitive impairment and strabismus

UniProtKB/Swiss-Prot : 73 Perrault syndrome 4: An autosomal recessive, sex-influenced disorder characterized by sensorineural deafness in both males and females, and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile.

Related Diseases for Perrault Syndrome 4

Diseases in the Perrault Syndrome family:

Perrault Syndrome 1 Perrault Syndrome 3
Perrault Syndrome 2 Perrault Syndrome 4
Perrault Syndrome 5 Perrault Syndrome 6

Diseases related to Perrault Syndrome 4 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 perrault syndrome 9.7 LARS2-AS1 LARS2
2 perrault syndrome 1 9.6 LARS2-AS1 LARS2
3 hydrops, lactic acidosis, and sideroblastic anemia 9.6 LARS2-AS1 LARS2
4 rare genetic deafness 9.5 LARS2-AS1 LARS2

Symptoms & Phenotypes for Perrault Syndrome 4

Human phenotypes related to Perrault Syndrome 4:

31 (show all 20)
# Description HPO Frequency HPO Source Accession
1 cognitive impairment 31 very rare (1%) HP:0100543
2 strabismus 31 very rare (1%) HP:0000486
3 cleft palate 31 very rare (1%) HP:0000175
4 increased circulating gonadotropin level 31 very rare (1%) HP:0000837
5 osteoporosis 31 very rare (1%) HP:0000939
6 cubitus valgus 31 very rare (1%) HP:0002967
7 primary amenorrhea 31 very rare (1%) HP:0000786
8 secondary amenorrhea 31 very rare (1%) HP:0000869
9 obesity 31 very rare (1%) HP:0001513
10 motor delay 31 very rare (1%) HP:0001270
11 disproportionate tall stature 31 very rare (1%) HP:0001519
12 gait ataxia 31 very rare (1%) HP:0002066
13 bicornuate uterus 31 very rare (1%) HP:0000813
14 decreased serum estradiol 31 very rare (1%) HP:0008214
15 hypoplasia of the uterus 31 very rare (1%) HP:0000013
16 progressive sensorineural hearing impairment 31 very rare (1%) HP:0000408
17 hypoplasia of the ovary 31 very rare (1%) HP:0008724
18 oligomenorrhea 31 very rare (1%) HP:0000876
19 tarlov cyst 31 very rare (1%) HP:0025643
20 premature ovarian insufficiency 31 HP:0008209

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Genitourinary Internal Genitalia Female:
small uterus
ovarian failure, premature
small ovaries

Head And Neck Ears:
hearing loss, more severe at lower frequencies
upsloping audiograms

Endocrine Features:
increased gonadotropin levels (in female patients)

Clinical features from OMIM®:

615300 (Updated 05-Mar-2021)

Drugs & Therapeutics for Perrault Syndrome 4

Search Clinical Trials , NIH Clinical Center for Perrault Syndrome 4

Genetic Tests for Perrault Syndrome 4

Genetic tests related to Perrault Syndrome 4:

# Genetic test Affiliating Genes
1 Perrault Syndrome 4 29 LARS2

Anatomical Context for Perrault Syndrome 4

MalaCards organs/tissues related to Perrault Syndrome 4:

40
Uterus, Ovary

Publications for Perrault Syndrome 4

Articles related to Perrault Syndrome 4:

# Title Authors PMID Year
1
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy. 6 57
32442335 2020
2
Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy. 6 57
30737337 2019
3
Biallelic mutations in LARS2 can cause Perrault syndrome type 2 with neurologic symptoms. 6 57
29205794 2018
4
First independent replication of the involvement of LARS2 in Perrault syndrome by whole-exome sequencing of an Italian family. 6 57
26657938 2016
5
Mutations in LARS2, encoding mitochondrial leucyl-tRNA synthetase, lead to premature ovarian failure and hearing loss in Perrault syndrome. 57 6
23541342 2013
6
LARS2-Perrault syndrome: a new case report and literature review. 57
32423379 2020
7
LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure. 6
26537577 2016
8
Perrault syndrome: Clinical report and retrospective analysis. 61
32767731 2020
9
Perrault syndrome with amenorrhea, infertility, Tarlov cyst, and degenerative disc. 61
31274036 2019

Variations for Perrault Syndrome 4

ClinVar genetic disease variations for Perrault Syndrome 4:

6 (show all 20)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 LARS2-AS1 NM_015340.4(LARS2):c.1565C>A (p.Thr522Asn) SNV Pathogenic 55871 rs199589947 3:45537808-45537808 3:45496316-45496316
2 LARS2 NM_015340.4(LARS2):c.1886C>T (p.Thr629Met) SNV Pathogenic 55872 rs398123036 3:45557610-45557610 3:45516118-45516118
3 LARS2-AS1 NM_015340.4(LARS2):c.1077del (p.Ile360fs) Deletion Pathogenic 55873 rs398123037 3:45527241-45527241 3:45485749-45485749
4 LARS2 NM_015340.4(LARS2):c.1912G>A (p.Glu638Lys) SNV Pathogenic 203991 rs864309643 3:45557636-45557636 3:45516144-45516144
5 LARS2 NM_015340.4(LARS2):c.899C>T (p.Thr300Met) SNV Pathogenic 203990 rs864309642 3:45518000-45518000 3:45476508-45476508
6 LARS2 NM_015340.4(LARS2):c.899C>T (p.Thr300Met) SNV Pathogenic 203990 rs864309642 3:45518000-45518000 3:45476508-45476508
7 LARS2 NM_015340.4(LARS2):c.371A>T (p.Asn124Ile) SNV Pathogenic 431125 rs776171893 3:45458981-45458981 3:45417489-45417489
8 LARS2 NM_015340.4(LARS2):c.1987C>T (p.Arg663Trp) SNV Pathogenic 431124 rs774649299 3:45557711-45557711 3:45516219-45516219
9 LARS2 NM_015340.4(LARS2):c.880G>A (p.Glu294Lys) SNV Pathogenic 992952 3:45517981-45517981 3:45476489-45476489
10 LARS2-AS1 NM_015340.4(LARS2):c.1556C>T (p.Thr519Met) SNV Pathogenic 992953 3:45537799-45537799 3:45496307-45496307
11 LARS2 NM_015340.4(LARS2):c.683G>A (p.Arg228His) SNV Pathogenic 691519 rs770440975 3:45500311-45500311 3:45458819-45458819
12 LARS2-AS1 NM_015340.4(LARS2):c.1115C>G (p.Ser372Ter) SNV Likely pathogenic 623147 rs1559484149 3:45527280-45527280 3:45485788-45485788
13 LARS2 NM_015340.4(LARS2):c.440A>C (p.Gln147Pro) SNV Likely pathogenic 691523 rs536853368 3:45459050-45459050 3:45417558-45417558
14 LARS2-AS1 NM_015340.4(LARS2):c.1607C>T (p.Pro536Leu) SNV Likely pathogenic 691524 rs1575292827 3:45537850-45537850 3:45496358-45496358
15 LARS2-AS1 NM_015340.4(LARS2):c.1237G>A (p.Glu413Lys) SNV Likely pathogenic 869196 3:45530302-45530302 3:45488810-45488810
16 LARS2 NM_015340.4(LARS2):c.1979A>T (p.Asp660Val) SNV Uncertain significance 982822 3:45557703-45557703 3:45516211-45516211
17 LARS2 NM_015340.4(LARS2):c.1814G>A (p.Arg605His) SNV Uncertain significance 504796 rs142665087 3:45554680-45554680 3:45513188-45513188
18 LARS2 NM_015340.4(LARS2):c.1784C>A (p.Ala595Asp) SNV Uncertain significance 689771 rs772859137 3:45554650-45554650 3:45513158-45513158
19 LARS2 NM_015340.4(LARS2):c.2269A>T (p.Met757Leu) SNV Uncertain significance 689772 rs1478071728 3:45561765-45561765 3:45520273-45520273
20 LARS2-AS1 NM_015340.4(LARS2):c.1692C>T (p.Ala564=) SNV Likely benign 226696 rs149911756 3:45542003-45542003 3:45500511-45500511

UniProtKB/Swiss-Prot genetic disease variations for Perrault Syndrome 4:

73
# Symbol AA change Variation ID SNP ID
1 LARS2 p.Thr522Asn VAR_070094 rs199589947

Expression for Perrault Syndrome 4

Search GEO for disease gene expression data for Perrault Syndrome 4.

Pathways for Perrault Syndrome 4

GO Terms for Perrault Syndrome 4

Sources for Perrault Syndrome 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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