PT - JOURNAL ARTICLE AU - Rashmi Dongerdiye AU - Pranoti Kamat AU - Punit Jain AU - Prashant Warang AU - Rati Devendra AU - Nilesh Wasekar AU - Ratna Sharma AU - Ketaki Mhaskar AU - Manisha R Madkaikar AU - Mamta V Manglani AU - Prabhakar S Kedar TI - Red cell adenylate kinase deficiency in India: identification of two novel missense mutations (c.71A>G and c.413G>A) AID - 10.1136/jclinpath-2019-205718 DP - 2019 Jun 01 TA - Journal of Clinical Pathology PG - 393--398 VI - 72 IP - 6 4099 - http://jcp.bmj.com/content/72/6/393.short 4100 - http://jcp.bmj.com/content/72/6/393.full SO - J Clin Pathol2019 Jun 01; 72 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.