Genetic Profiling of PHKA2 Gene and its Association with Udder Type Traits in Indian Dairy Cattle

Background: The experiment aimed to investigate polymorphisms in exon 2 of the PHKA2 gene and investigate the relationship between identified single nucleotide polymorphism and udder type traits in Sahiwal cows. Udder morphometry is being used as a forecaster of production performance in cows since older times. Finding the variants associated with these traits in largely variable region of PHKA2 gene can prove to be highly beneficial. Methods: DNA isolated from Sahiwal cows was analysed by DNA sequencing. Nine udder type and five teat types were measured for each animal according to procedure followed by International committee of animal recording (2012). Result: Three SNPs g.124497381C greater than T, X:124497248 G greater than A and X:124497189 C greater than T were identified. Recessive homozygotes were negligible as mutant allele exhibited very low ranging frequency (from 0.02 to 0.08) for the targeted loci. Identified point mutation g.124497381C greater than T was found to be significantly (p less than 0.05) associated with distance between teats and central ligament, SNP X: 124497248G greater than A with rear udder width, fore udder attachment, udder depth, udder length and teat length (p less than 0.05) and SNP X: 124497189 C greater than T with udder length and rear udder height (p less than 0.05). Interaction of identified SNPs and udder traits highlighted the gene’s potential as a candidate gene for selecting for conformation traits in Indian Sahiwal cattle.

Glycogen Storage Disease Type IX due to a Novel Mutation in PHKA2 Gene

We report a case of a 17-month-old male with a history of developmental delay with poor muscle control, hepatomegaly, and transaminitis. Ultrasound of abdomen revealed hepatomegaly with a liver span of 13 cm, homogeneous parenchyma, and normal spleen size. Liver and muscle biopsies were obtained: the liver biopsy revealed distended hepatocytes with excessive glycogen accumulation and fine septate fibrosis. Biopsy of the right vastus lateralis muscle showed focal swollen glycogen containing mitochondria. For the developmental delay, a chromosomal microrarray was ordered. The chromosomal microarray revealed the patient to have 1q21 duplication syndrome and 16p11.2 deletion syndrome. Given the liver and muscle biopsy findings, a glycogen storage disease panel was sent which identified the patient to be hemizygous for a variant of uncertain significance denoted as p.Gly 131Val, c.392G > T in the PHKA2 gene. PKHA2 gene encodes the alpha subunit of hepatic phosphorylase kinase. This change in the PHKA2 gene was in a highly conserved region and had been reported in another patient with decreased enzymatic activity of the phosphorylase kinase and who had symptoms of GSD IX. Based on this, the patient was started on treatment for GSD IX, and his family met with a dietician.

Glycogenosis type IX in a 9-year-old child

Since the age of 1 year, a child presented with hypoglycemic conditions accompanied by ketosis as well as periodic hyperglycemia, for which reason he was hospitalized to the Pediatric Endocrinology Department of the Mirotvortsev Saratov Clinical Hospital. At the hospital, the child underwent a comprehensive examination that excluded diseases such as hyperinsulinism and diabetes mellitus. In the Laboratory of Hereditary Diseases of Metabolism of the Medical Genetics Research Center, a hemizygotic mutation in the PHKA2 gene (glycogenosis type IX) was detected. The mother was also detected with the heterozygous mutation c.226G>A (p.E76K in the PHKA2 gene). Based on the results of the genetic examination of the child and mother, the patient was finally diagnosed with glycogenosis type IX. The patient was put on an individualized protein diet avoiding edible sugar and fatty foods; corn starch (30 g every 6 h and overnight) was recommended. Strict adherence to the diet resulted in less frequent seizures and decreased severity of episodes.