OMIM ID:
Cone-Rod Dystrophy With Decreased Male Fertility
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Features of a cone dystrophy appear first followed by rod damage although the course of degeneration is variable. Poor vision may be present in some individuals in the first years of life but has a later onset in others. Evidence for rod dysfunction appears later in most patients.
A hyperfluorescent area centered on the fovea can often be seen although there may be patchy areas elsewhere in the fundus. Foveal atrophy is present in individuals generally after the 5th decade of life. Full field ERG shows reduced or absent cone responses with variable rod responses with more pronounced changes in older individuals. Variable pigmentation can be seen in the peripapillary area.
Systemic Features
The only systemic abnormality thus far identified is a reduction in sperm count and reduced motility. The resulting loss of fertility, however, occurs only in male patients with truncating variants in TTLL5 and not in those with missense mutations according to the most recent studies.
Genetics
Inheritance
This autosomal recessive condition results from homozygous or compound heterozygous mutations in the TTLL5 gene (14q24.3). TTLL5 is localized at the base of the spermatozoal axoneme and at the basal body of the cilia in photoreceptors.
Interestingly, male mice with mutations in this gene have reductions in sperm motility with evident disruption in the formation of sperm tails.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.