Amish, Mennonite, and Hutterite
Genetic Disorder Database

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, hypotonicity, developmental regression, developmental delay/mental retardation, ophthalmoplegia, respiratory and bulbar dysfuction, ataxia 
Seen In: Amish
Old Order Mennonite
Old Colony Mennonite
Unknown/Other Mennonite
Hutterite
Remarks:

Testing is available at LHSC.

 

Mutations
1   Hutterite  
Gene: NDUFS4
Base Change:
Amino Acid Change: c.393dupA
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:
Last updated: 2019-07-03 

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 
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 
Personal communication; seen at CSC.  

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