Prenatal diagnosis for a novel homozygous mutation in PKLR gene in an Indian family

Abstract

This case reiterates the importance of application of molecular genetics in clinical practice and prenatal diagnosis especially for rare, incurable genetic disorders.

Spectrum of novel mutations in the human PKLR gene in pyruvate kinase‐deficient Indian patients with heterogeneous clinical phenotypes

“…Interestingly, two other mutations 884C.T and 943G.A previously reported in individuals originating from the Indian subcontinent were not detected in our cases (29). In two families, having a homozygous child with 992A.G and 1436G.A mutations, respectively, prenatal diagnosis was performed in the subsequent pregnancies, and the babies were found to be heterozygous (30,31). We found another novel homozygous mutation, 1220A.G, resulting in an amino acid substitution changing glutamate to glycine at amino acid position 407 in the A domain.…”

“…After excluding other common causes like thalassaemia, sickle-cell anaemia, HS, G6PD deficiency and autoimmune haemolytic anaemia, these cases were investigated for various enzymopathies (24). In two families, having a homozygous child with 992A.G and 1436G.A mutations, respectively, prenatal diagnosis was performed in the subsequent pregnancies, and the babies were found to be heterozygous (30,31). Except for the 1456C.T mutation, the other two mutations were not detected in the Indian population.…”

Pyruvate kinase deficiency

“…Among the 180 different mutations so far identified in the PK-LR gene, [13][14][15][16] mostly missense, 1529A is the most common in the USA, and Northern and Central Europe, 1456T is prevalent in Southern Europe, and 1468T in Asia. 6 Molecular studies indicate that a severe syndrome is commonly associated with disruptive mutations and with missense mutations more or less directly involving the active site or protein stability.…”