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Novel POMGNT1 point mutations and intragenic rearrangements associated with muscle-eye-brain disease.

Saredi S, Ardissone A, Ruggieri A, Mottarelli E, Farina L, Rinaldi R, Silvestri E, Gandioli C, D'Arrigo S, Salerno F, Morandi L, Grammatico P, Pantaleoni C, Moroni I, Mora M - J. Neurol. Sci. (2012)

Bottom Line: We identify two new point mutations (c.643C>T, c.1863delC), one new intragenic rearrangement (deletion of exons 2-8), and a new intron retention (between exons 21 and 22) resulting from a known point mutation c.1895+1G>T.POMGNT1 protein analysis in 3 patients showed that the severity of the phenotype does not correlate with protein expression.Cerebral MRI is important for identifying MEB and α-dystroglycanopathy phenotypes in children and foetuses, and hence for directing the genetic analysis.

View Article: PubMed Central - PubMed

Affiliation: Division of Neuromuscular Diseases and Neuroimmunology, Foundation Neurological Institute C. Besta, Milano, Italy.

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MRI of patient 1 (A–D) patient 2 (E, F) and foetus 1 (G, H). (A) Midline sagittal T1-weighted image showing callosal hypogenesis and hypoplastic pons; (B) axial T1-IR weighted image revealing multiple cerebellar cysts; (C, D) axial T2-weighted images showing irregularity of cortex-white matter junction in frontal lobes, indicative of polymicrogyria, and irregular projections of cortex into the underlying white matter in the temporo-parietal-occipital regions indicative of cobblestone lissencephaly. Widespread white matter hyperintensity is also present. (E) Midline sagittal T1-weighted image showing partial callosal agenesis, hypoplastic brainstem and pons and fused colliculi (note small posterior fossa and tonsillar ectopia); and (F) axial T2-weighted image demonstrating malformed temporo-occipital-parietal lobes, indicative of polymicrogyria, associated with abnormally enlarged ventricular spaces. (G) Axial T2-weighted image showing marked ventricular enlargement and cerebral cortex thinning; and (H) sagittal T2-weighted image showing hypoplastic and dysmorphic brainstem with posterior kinking (20 weeks).
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f0005: MRI of patient 1 (A–D) patient 2 (E, F) and foetus 1 (G, H). (A) Midline sagittal T1-weighted image showing callosal hypogenesis and hypoplastic pons; (B) axial T1-IR weighted image revealing multiple cerebellar cysts; (C, D) axial T2-weighted images showing irregularity of cortex-white matter junction in frontal lobes, indicative of polymicrogyria, and irregular projections of cortex into the underlying white matter in the temporo-parietal-occipital regions indicative of cobblestone lissencephaly. Widespread white matter hyperintensity is also present. (E) Midline sagittal T1-weighted image showing partial callosal agenesis, hypoplastic brainstem and pons and fused colliculi (note small posterior fossa and tonsillar ectopia); and (F) axial T2-weighted image demonstrating malformed temporo-occipital-parietal lobes, indicative of polymicrogyria, associated with abnormally enlarged ventricular spaces. (G) Axial T2-weighted image showing marked ventricular enlargement and cerebral cortex thinning; and (H) sagittal T2-weighted image showing hypoplastic and dysmorphic brainstem with posterior kinking (20 weeks).

Mentions: All 3 cases had severe psychomotor delay; generalized epileptic seizures eventually controlled with antiepileptic drugs also developed in all. CK levels were moderately elevated. Cerebral magnetic resonance imaging (MRI) showed cerebellar cysts or cerebellar hypoplasia and widespread abnormalities in the cerebral cortex, in all 3 cases (Fig. 1). Muscle biopsy revealed increased mainly perimysial connective tissue, fibre diameter variability, and a few degenerating fibres, in all cases.


Novel POMGNT1 point mutations and intragenic rearrangements associated with muscle-eye-brain disease.

Saredi S, Ardissone A, Ruggieri A, Mottarelli E, Farina L, Rinaldi R, Silvestri E, Gandioli C, D'Arrigo S, Salerno F, Morandi L, Grammatico P, Pantaleoni C, Moroni I, Mora M - J. Neurol. Sci. (2012)

MRI of patient 1 (A–D) patient 2 (E, F) and foetus 1 (G, H). (A) Midline sagittal T1-weighted image showing callosal hypogenesis and hypoplastic pons; (B) axial T1-IR weighted image revealing multiple cerebellar cysts; (C, D) axial T2-weighted images showing irregularity of cortex-white matter junction in frontal lobes, indicative of polymicrogyria, and irregular projections of cortex into the underlying white matter in the temporo-parietal-occipital regions indicative of cobblestone lissencephaly. Widespread white matter hyperintensity is also present. (E) Midline sagittal T1-weighted image showing partial callosal agenesis, hypoplastic brainstem and pons and fused colliculi (note small posterior fossa and tonsillar ectopia); and (F) axial T2-weighted image demonstrating malformed temporo-occipital-parietal lobes, indicative of polymicrogyria, associated with abnormally enlarged ventricular spaces. (G) Axial T2-weighted image showing marked ventricular enlargement and cerebral cortex thinning; and (H) sagittal T2-weighted image showing hypoplastic and dysmorphic brainstem with posterior kinking (20 weeks).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3405532&req=5

f0005: MRI of patient 1 (A–D) patient 2 (E, F) and foetus 1 (G, H). (A) Midline sagittal T1-weighted image showing callosal hypogenesis and hypoplastic pons; (B) axial T1-IR weighted image revealing multiple cerebellar cysts; (C, D) axial T2-weighted images showing irregularity of cortex-white matter junction in frontal lobes, indicative of polymicrogyria, and irregular projections of cortex into the underlying white matter in the temporo-parietal-occipital regions indicative of cobblestone lissencephaly. Widespread white matter hyperintensity is also present. (E) Midline sagittal T1-weighted image showing partial callosal agenesis, hypoplastic brainstem and pons and fused colliculi (note small posterior fossa and tonsillar ectopia); and (F) axial T2-weighted image demonstrating malformed temporo-occipital-parietal lobes, indicative of polymicrogyria, associated with abnormally enlarged ventricular spaces. (G) Axial T2-weighted image showing marked ventricular enlargement and cerebral cortex thinning; and (H) sagittal T2-weighted image showing hypoplastic and dysmorphic brainstem with posterior kinking (20 weeks).
Mentions: All 3 cases had severe psychomotor delay; generalized epileptic seizures eventually controlled with antiepileptic drugs also developed in all. CK levels were moderately elevated. Cerebral magnetic resonance imaging (MRI) showed cerebellar cysts or cerebellar hypoplasia and widespread abnormalities in the cerebral cortex, in all 3 cases (Fig. 1). Muscle biopsy revealed increased mainly perimysial connective tissue, fibre diameter variability, and a few degenerating fibres, in all cases.

Bottom Line: We identify two new point mutations (c.643C>T, c.1863delC), one new intragenic rearrangement (deletion of exons 2-8), and a new intron retention (between exons 21 and 22) resulting from a known point mutation c.1895+1G>T.POMGNT1 protein analysis in 3 patients showed that the severity of the phenotype does not correlate with protein expression.Cerebral MRI is important for identifying MEB and α-dystroglycanopathy phenotypes in children and foetuses, and hence for directing the genetic analysis.

View Article: PubMed Central - PubMed

Affiliation: Division of Neuromuscular Diseases and Neuroimmunology, Foundation Neurological Institute C. Besta, Milano, Italy.

Show MeSH
Related in: MedlinePlus