RT Journal Article
SR Electronic
T1 Red cell adenylate kinase deficiency in India: identification of two novel missense mutations (c.71A>G and c.413G>A)
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 393
OP 398
DO 10.1136/jclinpath-2019-205718
VO 72
IS 6
A1 Rashmi Dongerdiye
A1 Pranoti Kamat
A1 Punit Jain
A1 Prashant Warang
A1 Rati Devendra
A1 Nilesh Wasekar
A1 Ratna Sharma
A1 Ketaki Mhaskar
A1 Manisha R Madkaikar
A1 Mamta V Manglani
A1 Prabhakar S Kedar
YR 2019
UL http://jcp.bmj.com/content/72/6/393.abstract
AB Adenylate kinase (AK) deficiency is a rare erythroenzymopathy associated with hereditary nonspherocytic haemolytic anaemia along with mental/psychomotor retardation in few cases. Diagnosis of AK deficiency depends on the decreased level of enzyme activity in red cell and identification of a mutation in the AK1 gene. Until, only eight mutations causing AK deficiency have been reported in the literature. We are reporting two novel missense mutation (c.71A > G and c.413G > A) detected in the AK1 gene by next-generation sequencing (NGS) in a 6-year-old male child from India. Red cell AK enzyme activity was found to be 30% normal. We have screened a total of 32 family members of the patient and showed reduced red cell enzyme activity and confirm mutations by Sanger’s sequencing. On the basis of Sanger sequencing, we suggest that the proband has inherited a mutation in AK1 gene exon 4 c.71A > G (p.Gln24Arg) from paternal family and exon 6 c.413G > A (p.Arg138His) from maternal family. Bioinformatics tools, such as SIFT, Polymorphism Phenotyping v.2, Mutation Taster, MutPred, also confirmed the deleterious effect of both the mutations. Molecular modelling suggests that the structural changes induced by p.Gln24Arg and p.Arg138His are pathogenic variants having a direct impact on the structural arrangement of the region close to the active site of the enzyme. In conclusion, NGS will be the best solution for diagnosis of very rare disorders leading to better management of the disease. This is the first report of the red cell AK deficiency from the Indian population.