Heimler syndrome is a rare autosomal recessive condition characterized by sensorineural hearing loss,
amelogenesis imperfecta
Amelogenesis imperfecta (AI) is a congenital disorder which presents with a rare abnormal formation of the enamel or external layer of the crown of teeth, unrelated to any systemic or generalized conditions. Enamel is composed mostly of mineral, ...
, nail abnormalities and occasional or late-onset retinal pigmentation
Signs/symptoms
This condition is characterised by sensorineural hearing loss, enamel hypoplasia of the secondary dentition, nail abnormalities and occasional or late-onset retinal pigmentation abnormalities.
Genetics
This condition is caused by mutations in
peroxisomal
A peroxisome () is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen per ...
biogenesis factor 1 (
PEX1
Peroxisome biogenesis factor 1, also known as PEX1, is a protein which in humans is encoded by the ''PEX1'' gene.
This gene encodes a member of the AAA protein family, a large group of ATPases associated with diverse cellular activities. This pr ...
) or peroxisomal biogenesis factor 6 (
PEX6
Peroxisome assembly factor 2 is a protein that in humans is encoded by the ''PEX6'' gene. PEX6 is an AAA ATPase that localizes to the peroxisome. PEX6 forms a hexamer with PEX1 and is recruited to the membrane by PEX26.
Function
From yeast t ...
) genes.
[Ratbi I, Falkenberg KD, Sommen M, Al-Sheqaih N, Guaoua S, Vandeweyer G, Urquhart JE, Chandler KE, Williams SG, Roberts NA, El Alloussi M, Black GC, Ferdinandusse S, Ramdi H, Heimler A, Fryer A, Lynch SA, Cooper N, Ong KR, Smith CE, Inglehearn CF, Mighell AJ, Elcock C, Poulter JA, Tischkowitz M, Davies SJ, Sefiani A, Mironov AA, Newman WG, Waterham HR, Van Camp G (2015) Heimler syndrome is caused by hypomorphic mutations in the peroxisome-biogenesis genes PEX1 and PEX6. Am J Hum Genet 97(4):535-545] These gene are involved in peroxisome biogenesis. PEX 1 is located on long arm of
chromosome 7
Chromosome 7 is one of the 23 pairs of chromosomes in humans, who normally have two copies of this chromosome. Chromosome 7 spans about 159 million base pairs (the building material of DNA) and represents between 5 and 5.5 percent of the total D ...
(7q21).2 PEX 6 is located on the short arm of
chromosome 6 (6p21). These genes encode AAA+
ATPases. They form part of the mechanism that shuttles the peroxisome targeting signal receptor protein
PEX5
Peroxisomal targeting signal 1 receptor (PTS1R) is a protein that in humans is encoded by the ''PEX5'' gene.
PTS1R is a peroxisomal targeting sequence involved in the specific transport of molecules for oxidation inside the peroxisome. SKL bind ...
back to the cytosol after release of its protein cargo within the peroxisomal lumen.
Diagnosis
The diagnosis is made on clinical grounds and confirmed by gene sequencing.
Treatment
There is no treatment for this condition known at present.
Prognosis
This condition tends to produce only mild abnormalities. Life expectancy is normal.
Epidemiology
This is rare disorder. Precise estimates of its prevalence are not known but it appears be to be < 1/10
6
History
This condition was first described in 1991.
[Heimler A, Fox JE, Hershey JE, Crespi P: Sensorineural hearing loss, enamel hypoplasia, and nail abnormalities in sibs. Am J Med Genet 39: 192–195]
References
External links
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Autosomal recessive disorders