Autosomal recessive retinitis pigmentosa caused by mutations in the MAK gene

Edwin M. Stone, Xunda Luo, Elise Héon, Byron L. Lam, Richard Weleber, Jennifer A. Halder, Louisa M. Affatigato, Jacqueline B. Goldberg, Alexander Sumaroka, Sharon B. Schwartz, Artur V. Cideciyan, Samuel G. Jacobson

Research output: Contribution to journalArticle

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Abstract

PURPOSE. To determine the disease expression in autosomal recessive (ar) retinitis pigmentosa (RP) caused by mutations in the MAK (male germ cell-associated kinase) gene. METHODS. Patients with RP and MAK gene mutations (n = 24; age, 32-77 years at first visit) were studied by ocular examination, perimetry, and optical coherence tomography (OCT). RESULTS. All but one MAK patient were homozygous for an identical truncating mutation in exon 9 and had Ashkenazi Jewish heritage. The carrier frequency of this mutation among 1207 unrelated Ashkenazi control subjects was 1 in 55, making it the most common cause of heritable retinal disease in this population and MAK-associated RP the sixth most common Mendelian disease overall in this group. Visual acuities could be normal into the eighth decade of life. Kinetic fields showed early loss in the superior-temporal quadrant. With more advanced disease, superior and midperipheral function was lost, but the nasal field remained. Only a central island was present at late stages. Pigmentary retinopathy was less prominent in the superior nasal quadrant. Rod-mediated vision was abnormal but detectable in the residual field; all patients had rod>cone dysfunction. Photoreceptor layer thickness was normal centrally but decreased with eccentricity. At the stages studied, there was no evidence of photoreceptor ciliary elongation. CONCLUSIONS. The patterns of disease expression in the MAK form of arRP showed some resemblance to patterns described in autosomal dominant RP, especially the form caused by RP1 mutations. The similarity in phenotypes is of interest, considering that there is experimental evidence of interaction between Mak and RP1 in the photoreceptor cilium.

Original languageEnglish (US)
Pages (from-to)9665-9673
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number13
DOIs
StatePublished - Dec 2011

Fingerprint

Retinitis Pigmentosa
Mutation
Genes
Nose
Night Vision
Retinal Diseases
Photoreceptor Cells
Visual Field Tests
Cilia
Optical Coherence Tomography
Mutation Rate
Islands
Germ Cells
Visual Acuity
Exons
Phosphotransferases
Phenotype
Population

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

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Autosomal recessive retinitis pigmentosa caused by mutations in the MAK gene. / Stone, Edwin M.; Luo, Xunda; Héon, Elise; Lam, Byron L.; Weleber, Richard; Halder, Jennifer A.; Affatigato, Louisa M.; Goldberg, Jacqueline B.; Sumaroka, Alexander; Schwartz, Sharon B.; Cideciyan, Artur V.; Jacobson, Samuel G.

In: Investigative Ophthalmology and Visual Science, Vol. 52, No. 13, 12.2011, p. 9665-9673.

Research output: Contribution to journalArticle

Stone, EM, Luo, X, Héon, E, Lam, BL, Weleber, R, Halder, JA, Affatigato, LM, Goldberg, JB, Sumaroka, A, Schwartz, SB, Cideciyan, AV & Jacobson, SG 2011, 'Autosomal recessive retinitis pigmentosa caused by mutations in the MAK gene', Investigative Ophthalmology and Visual Science, vol. 52, no. 13, pp. 9665-9673. https://doi.org/10.1167/iovs.11-8527
Stone, Edwin M. ; Luo, Xunda ; Héon, Elise ; Lam, Byron L. ; Weleber, Richard ; Halder, Jennifer A. ; Affatigato, Louisa M. ; Goldberg, Jacqueline B. ; Sumaroka, Alexander ; Schwartz, Sharon B. ; Cideciyan, Artur V. ; Jacobson, Samuel G. / Autosomal recessive retinitis pigmentosa caused by mutations in the MAK gene. In: Investigative Ophthalmology and Visual Science. 2011 ; Vol. 52, No. 13. pp. 9665-9673.
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abstract = "PURPOSE. To determine the disease expression in autosomal recessive (ar) retinitis pigmentosa (RP) caused by mutations in the MAK (male germ cell-associated kinase) gene. METHODS. Patients with RP and MAK gene mutations (n = 24; age, 32-77 years at first visit) were studied by ocular examination, perimetry, and optical coherence tomography (OCT). RESULTS. All but one MAK patient were homozygous for an identical truncating mutation in exon 9 and had Ashkenazi Jewish heritage. The carrier frequency of this mutation among 1207 unrelated Ashkenazi control subjects was 1 in 55, making it the most common cause of heritable retinal disease in this population and MAK-associated RP the sixth most common Mendelian disease overall in this group. Visual acuities could be normal into the eighth decade of life. Kinetic fields showed early loss in the superior-temporal quadrant. With more advanced disease, superior and midperipheral function was lost, but the nasal field remained. Only a central island was present at late stages. Pigmentary retinopathy was less prominent in the superior nasal quadrant. Rod-mediated vision was abnormal but detectable in the residual field; all patients had rod>cone dysfunction. Photoreceptor layer thickness was normal centrally but decreased with eccentricity. At the stages studied, there was no evidence of photoreceptor ciliary elongation. CONCLUSIONS. The patterns of disease expression in the MAK form of arRP showed some resemblance to patterns described in autosomal dominant RP, especially the form caused by RP1 mutations. The similarity in phenotypes is of interest, considering that there is experimental evidence of interaction between Mak and RP1 in the photoreceptor cilium.",
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T1 - Autosomal recessive retinitis pigmentosa caused by mutations in the MAK gene

AU - Stone, Edwin M.

AU - Luo, Xunda

AU - Héon, Elise

AU - Lam, Byron L.

AU - Weleber, Richard

AU - Halder, Jennifer A.

AU - Affatigato, Louisa M.

AU - Goldberg, Jacqueline B.

AU - Sumaroka, Alexander

AU - Schwartz, Sharon B.

AU - Cideciyan, Artur V.

AU - Jacobson, Samuel G.

PY - 2011/12

Y1 - 2011/12

N2 - PURPOSE. To determine the disease expression in autosomal recessive (ar) retinitis pigmentosa (RP) caused by mutations in the MAK (male germ cell-associated kinase) gene. METHODS. Patients with RP and MAK gene mutations (n = 24; age, 32-77 years at first visit) were studied by ocular examination, perimetry, and optical coherence tomography (OCT). RESULTS. All but one MAK patient were homozygous for an identical truncating mutation in exon 9 and had Ashkenazi Jewish heritage. The carrier frequency of this mutation among 1207 unrelated Ashkenazi control subjects was 1 in 55, making it the most common cause of heritable retinal disease in this population and MAK-associated RP the sixth most common Mendelian disease overall in this group. Visual acuities could be normal into the eighth decade of life. Kinetic fields showed early loss in the superior-temporal quadrant. With more advanced disease, superior and midperipheral function was lost, but the nasal field remained. Only a central island was present at late stages. Pigmentary retinopathy was less prominent in the superior nasal quadrant. Rod-mediated vision was abnormal but detectable in the residual field; all patients had rod>cone dysfunction. Photoreceptor layer thickness was normal centrally but decreased with eccentricity. At the stages studied, there was no evidence of photoreceptor ciliary elongation. CONCLUSIONS. The patterns of disease expression in the MAK form of arRP showed some resemblance to patterns described in autosomal dominant RP, especially the form caused by RP1 mutations. The similarity in phenotypes is of interest, considering that there is experimental evidence of interaction between Mak and RP1 in the photoreceptor cilium.

AB - PURPOSE. To determine the disease expression in autosomal recessive (ar) retinitis pigmentosa (RP) caused by mutations in the MAK (male germ cell-associated kinase) gene. METHODS. Patients with RP and MAK gene mutations (n = 24; age, 32-77 years at first visit) were studied by ocular examination, perimetry, and optical coherence tomography (OCT). RESULTS. All but one MAK patient were homozygous for an identical truncating mutation in exon 9 and had Ashkenazi Jewish heritage. The carrier frequency of this mutation among 1207 unrelated Ashkenazi control subjects was 1 in 55, making it the most common cause of heritable retinal disease in this population and MAK-associated RP the sixth most common Mendelian disease overall in this group. Visual acuities could be normal into the eighth decade of life. Kinetic fields showed early loss in the superior-temporal quadrant. With more advanced disease, superior and midperipheral function was lost, but the nasal field remained. Only a central island was present at late stages. Pigmentary retinopathy was less prominent in the superior nasal quadrant. Rod-mediated vision was abnormal but detectable in the residual field; all patients had rod>cone dysfunction. Photoreceptor layer thickness was normal centrally but decreased with eccentricity. At the stages studied, there was no evidence of photoreceptor ciliary elongation. CONCLUSIONS. The patterns of disease expression in the MAK form of arRP showed some resemblance to patterns described in autosomal dominant RP, especially the form caused by RP1 mutations. The similarity in phenotypes is of interest, considering that there is experimental evidence of interaction between Mak and RP1 in the photoreceptor cilium.

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