Here I present: “Autosomal Retinitis-Pigmentosa“, Victor McKusick, Mendelian Inheritance in Man’, 1966.
The same chromosomal locus (even the same gene) can produce both autosomal recessive and autosomal dominant disease, including retinal degenerations like RP. It’s uncommon, but absolutely real. The mechanism, not the map position, is what flips the inheritance.
Here’s the clean framework. How the same locus supports AR and AD inheritance.
1. Different mutation classes → different genetics. Same gene, different kinds of damage:
Mutation type
Typical inheritance
Why: Null / loss-of-function.
Autosomal recessive
One good copy is enough
Missense (toxic protein)
Autosomal dominant
Mutant protein harms cell
Dominant-negative
Autosomal dominant
Mutant poisons normal protein
Gain-of-function
Autosomal dominant
New toxic activity
So two alleles, same locus — radically different biology.
Retina is especially prone to this duality
Photoreceptors are:
post-mitotic
metabolically extreme
intolerant of protein stress
That’s why the retina repeatedly shows AR ↔ AD dual inheritance at the same gene.
Classic RP examples (outside chr10, just to prove the principle):
RHO → AD RP (toxic misfolding) and AR RP (null alleles)
PRPF31 → AD RP (haploinsufficiency)
USH2A → AR RP, but dominant modifiers reported
So the pattern is established biology, not an exception.
Now apply this to chromosome 10 loci
🧬 RGR (10q23.1)
Known: Autosomal recessive RP44
Mechanistic logic:
Biallelic loss → retinoid cycle failure
Heterozygous carriers usually asymptomatic
But:
A toxic missense affecting chromophore binding could plausibly act dominant
Retina/RPE interface is sensitive to dominant-negative retinoid defects
👉 AR proven, AD biologically plausible (not yet well documented)
🧬 HK1 (10q21.3–q22.1)
Reported: Autosomal dominant RP linkage
Mechanism:
Not simple loss-of-function
Likely metabolic misregulation / toxic gain-of-function
Meanwhile:
Complete HK1 loss is lethal → explains absence of classic AR RP cases
👉 Same locus, but only dominant disease survives to be seen
🧬 PRPF18 (10q24.32)
Known: Autosomal recessive RP
Spliceosome genes are famous for duality:
AR → null alleles tolerated systemically
AD → haploinsufficiency or dominant-negative splice defects
Other PRPF genes already show AD RP
👉 AR confirmed; AD is mechanistically expected, even if rare or unreported
Key principle (this is the punchline)
Inheritance is a property of the mutation, not the locus.
Same coordinates.
Same gene.
Different alleles → different population genetics.
One-line summary
✅ Yes, autosomal recessive and dominant disease can arise from the same chromosomal locus
Retina genes do this more than almost any other tissue
Chromosome 10 RP loci (RGR, HK1, PRPF18) fit this rule cleanly
