TY - JOUR
T1 - Giant axonal neuropathy with novel GAN pathogenic variant in a patient of consanguineous origin from Poonch Jammu and Kashmir-India
AU - Mir, Yaser Rafiq
AU - Zeng, Xue
AU - Taneja, Atul K.
AU - Hassan, Asima
AU - Sheth, Jayesh
AU - Kuchay, Raja A.H.
N1 - Funding Information:
We are extremely thankful to the patient and his family for participation in this study. We thank reviewers for their positive role in improving this manuscript. We thank Prof. Iqbal Parvez, DAA, BGSBU for his inputs. We thank Dr. Susheel Verma (Associate Professor, SB&B), Dr. Javid Reshi (Medical Officer, BGSBU), Dr. A.A Shah (Associate Professor, SB&B), Dr. Tanvir-ul-Hassn, and Dr. Saima Aslam for their timely inputs. We are thankful to Mr. Talat for his timely services. Laboratory of Dr. Raja Amir was supported by UGC Start Up grant, New Delhi, India.
Funding Information:
We are extremely thankful to the patient and his family for participation in this study. We thank reviewers for their positive role in improving this manuscript. We thank Prof. Iqbal Parvez, DAA, BGSBU for his inputs. We thank Dr. Susheel Verma (Associate Professor, SB&B), Dr. Javid Reshi (Medical Officer, BGSBU), Dr. A.A Shah (Associate Professor, SB&B), Dr. Tanvir-ul-Hassn, and Dr. Saima Aslam for their timely inputs. We are thankful to Mr. Talat for his timely services. Laboratory of Dr. Raja Amir was supported by UGC Start Up grant, New Delhi, India.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.
PY - 2021/2
Y1 - 2021/2
N2 - Giant axonal neuropathy (GAN) is a severe and rare autosomal recessive neurodegenerative disorder of childhood affecting both the peripheral and central nervous systems (CNS). It is caused by mutations in the GAN (gigaxonin) gene linked to chromosome 16q24. Here, we present a 15-year-old male patient with GAN from a consanguineous family of Poonch, Jammu and Kashmir (J&K)-India. Whole-exome sequencing (WES) was employed to unravel the genetic cause of GAN in the proband. Pathogenic variant identified with WES was confirmed in other affected sibling using Sanger sequencing. Magnetic resonance imaging (MRI) and detailed clinical investigation was also carried out on proband. WES revealed a novel homozygous stopgain GAN mutation (NM_022041, c.C1028G, p.S343X) in the patient. MRI of brain displayed bilateral symmetrical confluent areas of deep white matter signal changes affecting periventricular regions (with sparing of subcortical U-fibers), posterior limbs of internal capsules, thalami, external capsules, and semioval centers. The patient was initially suspected to be a case of metachromatic leukodystrophy. However, WES analysis revealed a pathogenic variant in GAN gene as causative. No other pathogenic variant relevant to any other type of dystrophy was reported in WES. Our findings extend the geographical distribution of GAN to even a very remote region in India, extend the mutational and imaging spectrum of GAN and substantiate the need for introducing genetic testing and counselling in primary referral centers/district hospitals in India.
AB - Giant axonal neuropathy (GAN) is a severe and rare autosomal recessive neurodegenerative disorder of childhood affecting both the peripheral and central nervous systems (CNS). It is caused by mutations in the GAN (gigaxonin) gene linked to chromosome 16q24. Here, we present a 15-year-old male patient with GAN from a consanguineous family of Poonch, Jammu and Kashmir (J&K)-India. Whole-exome sequencing (WES) was employed to unravel the genetic cause of GAN in the proband. Pathogenic variant identified with WES was confirmed in other affected sibling using Sanger sequencing. Magnetic resonance imaging (MRI) and detailed clinical investigation was also carried out on proband. WES revealed a novel homozygous stopgain GAN mutation (NM_022041, c.C1028G, p.S343X) in the patient. MRI of brain displayed bilateral symmetrical confluent areas of deep white matter signal changes affecting periventricular regions (with sparing of subcortical U-fibers), posterior limbs of internal capsules, thalami, external capsules, and semioval centers. The patient was initially suspected to be a case of metachromatic leukodystrophy. However, WES analysis revealed a pathogenic variant in GAN gene as causative. No other pathogenic variant relevant to any other type of dystrophy was reported in WES. Our findings extend the geographical distribution of GAN to even a very remote region in India, extend the mutational and imaging spectrum of GAN and substantiate the need for introducing genetic testing and counselling in primary referral centers/district hospitals in India.
KW - Consanguineous family
KW - Giant axonal neuropathy
KW - India
KW - Jammu and Kashmir
KW - Whole exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85100409408&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85100409408&partnerID=8YFLogxK
U2 - 10.1007/s11033-021-06166-7
DO - 10.1007/s11033-021-06166-7
M3 - Article
C2 - 33528728
AN - SCOPUS:85100409408
SN - 0301-4851
VL - 48
SP - 1607
EP - 1614
JO - Molecular Biology Reports
JF - Molecular Biology Reports
IS - 2
ER -