Mitochondrial mutations associated with syndromic hearing impairment

Gene

Mutation

Phenotype

References

Omim entree

MTTL1 

3243A->G

MELAS and MIDD

Goto et al., 1990
van den Ouweland et al., 1992

540000 (MELAS)
590050 (MTTL1)

MTTK 

8344A->G

8356T->C

8296A->G

MERRF

MERRF

MIDD

Shoffner et al., 1990

Zeviani et al., 1993

Kameoka et al., 1998

545000 (MERFF)
590060 (MTTK)

590060 (MTTK)

MTTS1 

7512T->C

progressive myoclonic epilepsy, ataxia and hearing impairment

Jaksch et al., 1998b

590080 (MTTS1)

Several

Large deletions

KSS 

Moraes et al., 1989

530000 (KSS)

Several

Large deletion/duplication

MIDD

Ballinger et al., 1992

520000 (MIDD)

MTTE

14709T->C

MIDD

Hao et al., 1995

590025 (MTTE)

 

 

 

 

 



The most frequently seen forms of mitochondrial syndromic hearing impairment comprise acquired mitochondrial neuromuscular syndromes such as KSS, MERFF and MELAS, as well as maternally inherited diabetes mellitus  and deafness (MIDD). Next to large rearrangements involving several genes, all mitochondrial mutations leading to syndromic hearing impairment are point mutations in tRNA genes; no point mutations in genes coding for protein have been found.
  • Kearns-Sayre Syndrome (KSS) : Progressive external ophthalmoplegia (PEO) and retinopathy manifest before the age of 20; ataxia, heart block or CSF protein elevation subsequently develop. Sensorineural hearing loss can occur as part of the phenotype.
  • Myoclonic epilepsy and ragged red fibers (MERRF): The phenotype is characterized by myoclonus, epilepsy and ataxia, although dementia, optic atrophy and deafness frequently occur. The degree of hearing loss is variable.
  • Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS): MELAS is a childhood disease that is characterized by intermittent vomiting, proximal limb weakness and recurrent cerebral insults resembling strokes and causing hemiparesis and cortical blindness. MELAS is frequently associated with short stature. The wide range of clinical signs and symptoms include hearing loss in approximately 30% of affected persons.
  • Maternally inherited diabetes and deafness (MIDD). Several families have been described with diabetes mellitus and sensorineural hearing loss, in which mitochondrial mutations have been found. The most frequently found mutation is the 3243A->G mutation, also found in MELAS. In population studies of diabetics, the 3243A->G mutation has been found in a few percent of patients ( Kadowaki et al, 1994 , Newkirk et al, 1997 ).