**6. Conclusion**

**Table 2** consists of previously published mutations in some Fe-S cluster genes.

*BOLA3* Missense c.287A>G p.His96Arg Lethal infantile mitochondrial

*BOLA3* Microdeletion c.225\_229delGAGAA; p. Lys75\* Lethal infantile mitochondrial

*BOLA3* Microduplication c.123dupA Combined respiratory chain

*IBA57* Missense c.313C>T; p.Arg105Trp Leukodystrophy with acute

*IBA57* Missense c.316A>G; p.Thr106Ala Leukodystrophy with acute

*IBA57* Missense c.586T>G; p.Trp196Gly Leukodystrophy,

*IBA57* Missense c.686C>T; p.Pro229Leu Leukodystrophy,

*IBA57* Missense c.706C>T; p.Pro236Ser Leukodystrophy with acute

*IBA57* Missense c.757G>C; p.Val253Leu Leukodystrophy with acute

*IBA57* Small insertion c.87\_88ins11 Leukodystrophy with acute

*NFU1* Missense c.565G>A; p.Gly189Arg Leukoencephalopathy with

*IBA57* Missense c.941A>C; p.Gln314Pro Myopathy and encephalopathy Ajit Bolar et al.

*IBA57* Splice IVS2 ds A-G-2; c.678A>G Spastic paraplegia Lossos et al.

*NFU1* Missense c.62G>C; p.Arg21Pro NFU1 deficiency Ahting et al.

*NFU1* Missense c.544C>T; p.Arg182Trp NFU1 deficiency Ahting et al.

*BOLA3* Missense c.200T>A; p.Ile67Asn Multiple mitochondrial

244 Mitochondrial Diseases

**Gene Mutation type Mutation Disease and phenotype References**

*BOLA3* Nonsense c.136C>T; p.Arg46\* Nonketotic hyperglycinemia, Baker et al.

*IBA57* Missense c.436C>T; p.Arg146Thr Leukodystrophy, fatal infantile Debray et al.

dysfunctions syndrome

and 2-oxoacid dehydrogenase

psychomotor regression

psychomotor regression

developmental delay, feeding problems and recurrent

developmental delay, feeding problems and recurrent

psychomotor regression and feeding difficulties

psychomotor regression

psychomotor regression

cysts and hyperglycinaemia

disorder

disorder

deficiency

vomiting

vomiting

Haack et al. [35]

Kohda et al. [37]

Kohda et al. [37]

Cameron et al.

Torraco et al. [39]

Torraco et al. [39]

Torraco et al. [39]

Torraco et al. [39]

Torraco et al. [39]

Torraco et al. [39]

Torraco et al. [39]

[15]

[41]

[42]

[42]

Nizon et al. [43–45]

[34]

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Iron-sulfur clusters are indispensable inorganic cofactors for biological function and involve in numerous cellular processes such as respiration and DNA repair. The cluster's assembly is complex and requires sophisticated protein machinery for its maturation and insertion into apoproteins. Since mitochondria is the main site for ISC biogenesis in human, any defect disturbing the biogenesis leads to a pathological outcome mostly appears as an mitochondrial entity in human. Currently, genetic alterations in several genes involving in ISC assembly and maturation have been linked to autosomal recessive mitochondrial human diseases known as multiple mitochondrial dysfunction syndromes. It is expected that more genes and alterations will appear in the literature related to ISC pathways. Moreover, there is still need to fully elucidate the phenotypic consequences of these genetic alterations and alteration of ISC pathways during the ISC related pathogenesis in human.

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