Table 1.

Molecular Genetic Testing Used in Single Large-Scale Mitochondrial DNA Deletion Syndromes

Deletion 1MethodProportion of Probands with an SLSMD Based on Clinical Phenotype
KSSPSCPEOLeigh syndrome
1.1- to 10-kb deletion of mitochondrial genome 2 Deletion/duplication analysis of the mitochondrial genome 3

100% 4

100%See footnote 5.<5% 6

KSS = Kearns-Sayre syndrome; CPEO = chronic progressive external ophthalmoplegia; PS = Pearson syndrome; SLSMD = single large-scale mitochondrial DNA deletion

1.

See Molecular Genetics for information on deletions detected in mitochondrial DNA (mtDNA). Duplications rarely occur with an SLSMD.

2.

More than 150 different SLSMDs have been associated with KSS [Damas et al 2014].

3.

Testing that identifies deletions/duplications not readily detectable by standard sequence analysis. Methods used may include a range of techniques including long-range PCR, quantitative PCR, and next-generation sequence analysis. Note: The mitochondrial genome has homology with regions of the nuclear genome; therefore, assays that depend on hybridization must be used with caution.

4.

The diagnosis of KSS requires identification of an SLSMD. A deletion of 4,977 bp known as m.8470_13446del4977 is the most common deletion [Schon 2003].

5.

Numerous pathogenic variants in either mtDNA or nuclear genes also cause CPEO that is often associated with other clinical manifestations. Identification of multiple (small- or large-scale) mtDNA deletions suggests a pathogenic variant in a nuclear gene (see Differential Diagnosis).

6.

An SLSMD can cause clinical and brain MRI findings consistent with Leigh syndrome. Leigh syndrome has more than 111 monogenic causes, including pathogenic variants in nuclear and mitochondrial genes (see ClinGen Expert Panel Curations).

From: Single Large-Scale Mitochondrial DNA Deletion Syndromes

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