Endgames Case Report

Patterns of inheritance, not always easily visible

BMJ 2013; 347 doi: http://dx.doi.org/10.1136/bmj.f6610 (Published 06 November 2013) Cite this as: BMJ 2013;347:f6610
  1. Kamron N Khan, Wellcome clinical fellow,
  2. Manir Ali, senior research fellow,
  3. James A Poulter, research fellow,
  4. Martin McKibbin, consultant ophthalmologist,
  5. Chris F Inglehearn, professor of molecular ophthalmology
  1. 1Section of Ophthalmology and Neuroscience, Leeds Institute of Molecular Medicine, University of Leeds, St James’s University Hospital, Leeds LS9 7TF, UK
  1. Correspondence to: K Khan medknk{at}leeds.ac.uk

This case report describes a boy with a rare ophthalmic disorder that uniquely demonstrates the complexities of clinically identifying the mode of disease inheritance. Although readers are unlikely to encounter this exact disorder, knowledge of the analytical approach needed to answer the questions posed will be of benefit to all specialties of medicine.

A 4 year old boy presented with symmetrical leucocoria (whitening of his ocular red reflex). His three younger siblings all had a normal eye examination, as did his parents (figure). He was diagnosed as having an inherited corneal disease (Schnyder corneal dystrophy) caused by mutations in the UBIAD1 gene. This gene encodes a protein that localises to the mitochondria and regulates cholesterol and lipid metabolism. In the disease state these products become abnormally deposited within the cornea, leading to opacification.

Family pedigree and genetic results. (A) Pedigree of the family showing affected (black symbols) and unaffected (unfilled symbols) family members. (B) Electropherograms showing wild-type (normal) sequences in both parents and an unaffected sibling alongside the mutated sequence of the affected child (II:1). For the affected child, two peaks are superimposed at the site of the mutation representing the presence of both the normal “G” allele and the mutant “A” allele

Questions

  • 1 What are the possible modes of inheritance in this case?

  • 2 How do we confirm the inheritance pattern?

  • 3 What are the implications for future (parental) pregnancies?

  • 4 What are the chances of the patient passing on this condition to his children?

Answers

1 What are the possible modes of inheritance in this case?

Short answer

All modes of inheritance are possible given the pedigree structure—autosomal dominant, autosomal recessive, X linked, mitochondrial, or sporadic.

Long answer

To date, Schnyder’s corneal dystrophy has been described only with autosomal dominant inheritance. Dominant disorders tend to have a strong family history, with at least one parent being affected. In some cases the disease may …

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