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Spinocerebellar ataxia 7 (SCA7) in Indian population: predilection of ATXN7-CAG expansion mutation in an ethnic population.

Faruq M, Srivastava AK, Singh S, Gupta R, Dada T, Garg A, Behari M, Mukerji M - Indian J. Med. Res. (2015)

Bottom Line: Analysis of the association of number of CAG repeats with disease onset revealed that <49 repeats were associated with earlier age at onset in South East Asians compared to European populations.Further analysis of CAG repeats from 21 diverse Indian populations showed pre-mutable repeats (28-34) alleles in the IE-N-LP2 population.Six of the nine families identified in this study belonged to the same ethnic population.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Neurosciences Centre, All India Institute of Medical Sciences (AIIMS), New Delhi, India.

ABSTRACT

Background & objectives: Spinocerebellar ataxia 7 (SCA7) is a rare form of neurodegenerative disorder with the clinical manifestation of cerebellar ataxia and retinal degeneration. In this study we describe the clinico-genetic characteristics of nine SCA7 families of Indian origin and cross compare these with other available worldwide studies.

Methods: Thirty five individuals from nine SCA7 families were clinico-genetically characterized and CAG repeat distribution analysis was carried out in 382 control DNA samples from healthy controls (derived from 21 diverse Indian populations based on ethnic and linguistic and geographical location).

Results: Of the nine families studied, 22 affected individuals and one asymptomatic carrier were identified. The average age at disease onset was 23.4±12.6 yr. The length of expanded CAG ranged from 40-94 with mean value of 53.2±13.9. The main clinical findings in affecteds individuals included cerebellar ataxia, and retinal degeneration along with hyper-reflexia (95%), slow saccades (85%) and spasticity (45%). Analysis of the association of number of CAG repeats with disease onset revealed that <49 repeats were associated with earlier age at onset in South East Asians compared to European populations. Further analysis of CAG repeats from 21 diverse Indian populations showed pre-mutable repeats (28-34) alleles in the IE-N-LP2 population. Six of the nine families identified in this study belonged to the same ethnic population.

Interpretations & conclusion: Our results show that presenece of SCA7 is relatively rare and confined to one ethnic group from Haryana region of India. We observed a homogeneous phenotypic expression of SCA7 mutation as described earlier and an earlier age of onset in our patients with CAG <49. The identification of pre-mutable allele in IE-N-LP2 suggests this population to be at the risk of SCA7.

No MeSH data available.


Related in: MedlinePlus

Fundus images and electroretinography (ERG) tracing of representative patients. Fundus showing (A) AT1795 case (CAG)43; bilateral fine mottling of retinal pigmentary epithelium (RPE), (B) AT1839(CAG)54; essential normal appearing fundus both eyes, (C) AT236 (CAG)49; macular atrophy and mild retinal arterial attenuation. ERG recording- (D) AT1795; B wave amplitude (A, μV) reduction RE/LE (38.09/38.06), latencies (L, milliseconds) RE/LE (120/116), (E) AT1839; B wave amplitude normal in RE and mildly reduced in LE (57.54), latencies RE/LE (140/150), (F) AT236; Extinguished response in both eyes.
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Figure 2: Fundus images and electroretinography (ERG) tracing of representative patients. Fundus showing (A) AT1795 case (CAG)43; bilateral fine mottling of retinal pigmentary epithelium (RPE), (B) AT1839(CAG)54; essential normal appearing fundus both eyes, (C) AT236 (CAG)49; macular atrophy and mild retinal arterial attenuation. ERG recording- (D) AT1795; B wave amplitude (A, μV) reduction RE/LE (38.09/38.06), latencies (L, milliseconds) RE/LE (120/116), (E) AT1839; B wave amplitude normal in RE and mildly reduced in LE (57.54), latencies RE/LE (140/150), (F) AT236; Extinguished response in both eyes.

Mentions: Paraclinical abnormalities in SCA7 patients: Among the paraclinical investigations performed (Table II), CT head/MRI-brain could be obtained for 11 patients and for 10 patients findings were consistent with olivopontocerebellar atrophy (OPCA) or cerebellar atrophy (Fig. 1). Electrophysiological studies conducted in seven patients showed no abnormality except for two patients where each showed a pattern suggestive of sensory-motor neuropathy and axonal neuropathy, respectively. Visual evoked potential (VEP) and brain stem auditory evoked response (BAER) studies conducted in four patients showed abnormality in two patients (CAG-49 and 43) and two had no impairment (CAG-40 each). Detailed fundus examination was carried out for seven affected individuals. One patient was (AT1839) found to have no gross changes in bilateral eyes despite subjective complaint of diminution of vision, the remaining patients showed degenerated retinal pigmentary epithelium (RPE) at the macular region (Fig. 2A–C.). Electroretinography recording was done for three patients including AT1839 and all showed abnormalities like extinguished response (AT236), reduced B-wave amplitude in Rt/Lt eyes 38.06/38.09 μV (AT1794) and mildly reduced B-wave amplitude in right eye-57.54/Lt eye-60.11 μV (AT1839) (Fig. 2D–F.).


Spinocerebellar ataxia 7 (SCA7) in Indian population: predilection of ATXN7-CAG expansion mutation in an ethnic population.

Faruq M, Srivastava AK, Singh S, Gupta R, Dada T, Garg A, Behari M, Mukerji M - Indian J. Med. Res. (2015)

Fundus images and electroretinography (ERG) tracing of representative patients. Fundus showing (A) AT1795 case (CAG)43; bilateral fine mottling of retinal pigmentary epithelium (RPE), (B) AT1839(CAG)54; essential normal appearing fundus both eyes, (C) AT236 (CAG)49; macular atrophy and mild retinal arterial attenuation. ERG recording- (D) AT1795; B wave amplitude (A, μV) reduction RE/LE (38.09/38.06), latencies (L, milliseconds) RE/LE (120/116), (E) AT1839; B wave amplitude normal in RE and mildly reduced in LE (57.54), latencies RE/LE (140/150), (F) AT236; Extinguished response in both eyes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4418155&req=5

Figure 2: Fundus images and electroretinography (ERG) tracing of representative patients. Fundus showing (A) AT1795 case (CAG)43; bilateral fine mottling of retinal pigmentary epithelium (RPE), (B) AT1839(CAG)54; essential normal appearing fundus both eyes, (C) AT236 (CAG)49; macular atrophy and mild retinal arterial attenuation. ERG recording- (D) AT1795; B wave amplitude (A, μV) reduction RE/LE (38.09/38.06), latencies (L, milliseconds) RE/LE (120/116), (E) AT1839; B wave amplitude normal in RE and mildly reduced in LE (57.54), latencies RE/LE (140/150), (F) AT236; Extinguished response in both eyes.
Mentions: Paraclinical abnormalities in SCA7 patients: Among the paraclinical investigations performed (Table II), CT head/MRI-brain could be obtained for 11 patients and for 10 patients findings were consistent with olivopontocerebellar atrophy (OPCA) or cerebellar atrophy (Fig. 1). Electrophysiological studies conducted in seven patients showed no abnormality except for two patients where each showed a pattern suggestive of sensory-motor neuropathy and axonal neuropathy, respectively. Visual evoked potential (VEP) and brain stem auditory evoked response (BAER) studies conducted in four patients showed abnormality in two patients (CAG-49 and 43) and two had no impairment (CAG-40 each). Detailed fundus examination was carried out for seven affected individuals. One patient was (AT1839) found to have no gross changes in bilateral eyes despite subjective complaint of diminution of vision, the remaining patients showed degenerated retinal pigmentary epithelium (RPE) at the macular region (Fig. 2A–C.). Electroretinography recording was done for three patients including AT1839 and all showed abnormalities like extinguished response (AT236), reduced B-wave amplitude in Rt/Lt eyes 38.06/38.09 μV (AT1794) and mildly reduced B-wave amplitude in right eye-57.54/Lt eye-60.11 μV (AT1839) (Fig. 2D–F.).

Bottom Line: Analysis of the association of number of CAG repeats with disease onset revealed that <49 repeats were associated with earlier age at onset in South East Asians compared to European populations.Further analysis of CAG repeats from 21 diverse Indian populations showed pre-mutable repeats (28-34) alleles in the IE-N-LP2 population.Six of the nine families identified in this study belonged to the same ethnic population.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Neurosciences Centre, All India Institute of Medical Sciences (AIIMS), New Delhi, India.

ABSTRACT

Background & objectives: Spinocerebellar ataxia 7 (SCA7) is a rare form of neurodegenerative disorder with the clinical manifestation of cerebellar ataxia and retinal degeneration. In this study we describe the clinico-genetic characteristics of nine SCA7 families of Indian origin and cross compare these with other available worldwide studies.

Methods: Thirty five individuals from nine SCA7 families were clinico-genetically characterized and CAG repeat distribution analysis was carried out in 382 control DNA samples from healthy controls (derived from 21 diverse Indian populations based on ethnic and linguistic and geographical location).

Results: Of the nine families studied, 22 affected individuals and one asymptomatic carrier were identified. The average age at disease onset was 23.4±12.6 yr. The length of expanded CAG ranged from 40-94 with mean value of 53.2±13.9. The main clinical findings in affecteds individuals included cerebellar ataxia, and retinal degeneration along with hyper-reflexia (95%), slow saccades (85%) and spasticity (45%). Analysis of the association of number of CAG repeats with disease onset revealed that <49 repeats were associated with earlier age at onset in South East Asians compared to European populations. Further analysis of CAG repeats from 21 diverse Indian populations showed pre-mutable repeats (28-34) alleles in the IE-N-LP2 population. Six of the nine families identified in this study belonged to the same ethnic population.

Interpretations & conclusion: Our results show that presenece of SCA7 is relatively rare and confined to one ethnic group from Haryana region of India. We observed a homogeneous phenotypic expression of SCA7 mutation as described earlier and an earlier age of onset in our patients with CAG <49. The identification of pre-mutable allele in IE-N-LP2 suggests this population to be at the risk of SCA7.

No MeSH data available.


Related in: MedlinePlus