A variation in PANK2 gene is causing Pantothenate kinase-associated Neurodegeneration in a family from Jammu and Kashmir – India

Abstract

Pantothenate kinase-associated neurodegeneration is a rare hereditary neurodegenerative disorder associated with nucleotide variation(s) in mitochondrial human Pantothenate kinase 2 (hPanK2) protein encoding PANK2 gene, and is characterized by symptoms of extra-pyramidal dysfunction and accumulation of non-heme iron predominantly in the basal ganglia of the brain. In this study, we describe a familial case of PKAN from the State of Jammu and Kashmir (J&K), India based on the clinical findings and genetic screening of two affected siblings born to consanguineous normal parents. The patients present with early-onset, progressive extrapyramidal dysfunction, and brain Magnetic Resonance imaging (MRI) suggestive of symmetrical iron deposition in the globus pallidi. Screening the PANK2 gene in the patients as well as their unaffected family members revealed a functional single nucleotide variation, perfectly segregating in the patient’s family in an autosomal recessive mode of inheritance. We also provide the results of in-silico analyses, predicting the functional consequence of the identified PANK2 variant.

Review: Understanding Rare Genetic Diseases in Low Resource Regions Like Jammu and Kashmir – India

“…In an independent study using a PCR-based Direct Sanger Sequencing Strategy, our research group has identified an autosomal recessive variant NM_153638.3:c.1069C>T (NP_705902.2:p.Arg357Trp; rs753376100) located in exon 3 of PANK2 gene in a clinically suspected familial case of neurodegenerative disorder "Pantothenate Kinase-Associated Neurodegeneration" (PKAN; OMIM# 234000) (Angural et al, 2017). PKAN is a progressive neurodegenerative disorder characterized by an abnormal accumulation of iron in the basal ganglia in brain and extra-pyramidal manifestation (Hayflick et al, 2003).…”

“…The variation identified is located at a highly conserved region in codon 357 of hPank2 protein and predicted to be pathogenic through in silico pathogenicity prediction tools. Through a comparative molecular dynamics study of the wild-type and variant hPank2 protein models, it was observed that the reported variation has rendered rigidity to the other highly dynamic protein structure which might have caused a functional compromise in hPank2 molecules (Angural et al, 2017).…”

PANK1 Is a Prognostic Biomarker Associated with Immune Infiltration of Clear Cell Renal Carcinoma

“…A previous study has shown that the PANK family gene is associated with the prognosis of acute myeloid leukemia and pointed out that high expression of PANK2 may have a good effect on the prognosis of AML, while high expression of PANK4 indicates a poor prognosis [21]. Pantothenate kinase-related neurodegenerative disease is a rare hereditary neurodegenerative disease associated with nucleotide variations in the PANK2 gene encoded by mitochondrial human pantothenate kinase 2(PANK2) protein [22]. Pantothenate kinase-related neurodegenerative diseases are the main symptoms of pan-extrapyramidal dysfunction and non-heme iron accumulation [22].…”

“…Pantothenate kinase-related neurodegenerative disease is a rare hereditary neurodegenerative disease associated with nucleotide variations in the PANK2 gene encoded by mitochondrial human pantothenate kinase 2(PANK2) protein [22]. Pantothenate kinase-related neurodegenerative diseases are the main symptoms of pan-extrapyramidal dysfunction and non-heme iron accumulation [22]. Although a few studies have suggested that PANK1 may play a key role in the occurrence of cancer [23], there is no literature exploring the correlation between PANK1 and renal clear cell carcinoma.…”

A rare PANK2 deletion in the first north African patient affected with pantothenate kinase associated neurodegeneration

“…The most common NBIA subtype, accounting for 35-50% of NBIA cases [2,3] is pantothenate kinase-associated neurodegeneration (PKAN) caused by biallelic variants in PANK2 (MIM #606157). PANK2 was the first causal gene discovered in NBIA, with cases reported from nearly all continents [1,[4][5][6][7][8].…”