Leigh Syndrome
| Disorder | |
|---|---|
| OMIM #: | #256000 (Click to access OMIM database) |
| Disorder: | Leigh Syndrome |
| Also known as: | NECROTIZING ENCEPHALOPATHY, INFANTILE SUBACUTE, OF LEIGH SNE |
| Clinical | |
| Phenotype: | typically affects infants and young children, hypotonia, ataxia, hyperreflexia, developmental delay, motor delay, lesions throughout central nervous system, ophthalmoplegia, respiratory and bulbar dysfuction, respiratory failure, lactic acidosis |
| Seen In: |
Amish Old Order Mennonite Old Colony Mennonite Unknown/Other Mennonite Hutterite |
| Remarks: | Testing is available at LHSC. Autosomal recessive |
| Mutations | |
| 1 Hutterite | |
| Gene: | NDUFS4 |
| Base Change: | c.393dupA |
| Amino Acid Change: | |
| ReferencesLal D, Becker K, Motameny S, Altmüller J, Thiele H, Nürnberg P, Ahting U, Rolinski B, Neubauer BA, Hahn A. (2013) Homozygous missense mutation of NDUFV1 as the cause of infantile bilateral striatal necrosis. Neurogenetics Feb;14(1):85-7. PubMed ID: 23334465 2 Old Colony Mennonite |
|
| Gene: | NDUFV1 |
| Base Change: | G>A, at nucleotide 640 |
| Amino Acid Change: | glu 214 --> lys |
| 3 Amish | |
| Gene: | ND5 |
| Base Change: | m.13513G>A |
| Amino Acid Change: | asp 393 --> asn |
| 4 Amish | |
| Gene: | NDUFAF2 |
| Base Change: | deletion of exon 2 |
| Amino Acid Change: | |
| 5 Old Order Mennonite | |
| Gene: | NDUFA12 |
| Base Change: | C>T, at nucleotide 178 |
| Amino Acid Change: | arg 60 --> term |
| 6 Hutterite | |
| Gene: | SQOR |
| Base Change: | G>A, at nucleotide 637 |
| Amino Acid Change: | glu 213 --> lys |
| Last updated: | 2022-12-07 |
| References |
|---|
| Bénit P, Chretien D, Kadhom N, de Lonlay-Debeney P, Cormier-Daire V, Cabral A, Peudenier S, Rustin P, Munnich A, Rötig A. (2001) Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex I deficiency. Am J Hum Genet Jun;68(6):1344-52. PubMed ID: 11349233 |
| Finsterer J, Zarrouk-Mahjoub S. (2017) NDUFS4-related Leigh syndrome in Hutterites. Am J Med Genet A May;173(5):1450-1451. PubMed ID: 28371352 |
| Friederich MW, Elias AF, Kuster, Laugwitz L, Larson AA, Landry AP, Ellwood-Digel L, Mirsky DM, Dimmock D, Haven J, Jiang H, MacLean KN, Styren K, Schoof J, Goujon L, Lefrancois T, Friederich M, Coughlin CR, Banerjee R, Haack TB, Van Hove JLK. (2020) Pathogenic variants in SQOR encoding sulfide:quinone oxidoreductase are a potentially treatable cause of Leigh disease. J Inherit Metab Dis Mar 11. doi: 10.1002/jimd.12232. PubMed ID: 32160317 |
| Ghaloul-Gonzalez L, Goldstein A, Vockley CW, Dobrowlski SF, Biery A, Irani A, Ibarra J, Morton DH, Mohsen AW, Vockley J. (2016) Mitochondrial respiratory chain disorders in the Old Order Amish population.. Mol Genet Metab S1096-7192. PubMed ID: 27344355 |
| Huntsman RJ, Sinclair DB, Bhargava R, Chan A. (2005) Atypical presentations of leigh syndrome: a case series and review. Pediatr Neurol 32(5):334-40. PubMed ID: 15866434 |
| Jaworski MA, Slater JD, Severini A, Hennig KR, Mansour G, Mehta JG, Jeske R, Schlaut J, Pak CY, Yoon JW. (1988) Unusual clustering of diseases in a Canadian Old Colony (Chortitza) Mennonite kindred and community. CMAJ 138(11):1017-25. PubMed ID: 3370569 |
| Lal D, Becker K, Motameny S, Altmüller J, Thiele H, Nürnberg P, Ahting U, Rolinski B, Neubauer BA, Hahn A. (2013) Homozygous missense mutation of NDUFV1 as the cause of infantile bilateral striatal necrosis. Neurogenetics Feb;14(1):85-7. PubMed ID: 23334465 |
| Lamont RE, Beaulieu CL, Bernier FP, Sparkes R, Innes AM, Jackel-Cram C, Ober C, Parboosingh JS, Lemire EG. (2017) A novel NDUFS4 frameshift mutation causes Leigh disease in the Hutterite population. Am J Med Genet A Mar;173(3):596-600. PubMed ID: 27671926 |
| Speer RR, Ezeanya UC, Beaudoin SJ, Glass KM, Oji-Mmuo CN. (2020) Term Neonate Presenting with the Combined Occurrence of Mucolipidosis Type II and Leigh Syndrome. J Pediatr Genet Jun;9(2):137-141. PubMed ID: 32341820 |
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