Scientists say they’ve solved an “80-year-old medical mystery” by showing how a specific form of kidney damage in children, which can be fatal in babies, isn't always caused by a gene mutation, but sometimes the gene's shape.
Known as infantile hypercalcemia type 1, the condition causes a build-up of calcium in the blood, leading to problems such as kidney damage and kidney stones.
Knowledge of the disease first came to light in the early 20th century when it was discovered that vitamin D from sunlight helped to prevent rickets. In a push to stamp out this bone condition, some foods became fortified with vitamin D, but it advertently led to a wave of baby deaths in the 1930s and ‘40s.
"Foods such as dairy products had been fortified with vitamin D, but it led to a number of baby deaths, and was eventually banned in many countries except for in breakfast cereals and margarine,” Dr Darrell Green, author of the new study from Norwich Medical School at the University of East Anglia in the UK, said in a statement.
A breakthrough came in 2011 when researchers showed that most people with the condition are born with a mutation in the CYP24A1 gene, which codes for an enzyme that helps control the amount of vitamin D available in the body. Oddly, however, around 10 percent of people with the disease do not appear to have the gene mutation in CYP24A1.
In a new study, scientists from the University of East Anglia looked to understand the minority of cases that don’t appear to have the mutated CYP24A1 gene.
They carried out next-generation genetic sequencing and computational modeling to study blood samples of 47 patients who fit into this “10 percent” of puzzling patients.
In these people, it appears their trouble with vitamin D didn’t stem from the gene mutation, but the physical shape of the CYP24A1 gene.
“A PhD student in my laboratory, Nicole Ball, carried out a more extensive genetic analysis of six patient blood samples and we found that the physical shape of the CYP24A1 gene in these apparent [infantile hypercalcemia type 1] patients is abnormal,” explained Dr Green.
“This tells us that gene shape is important in gene regulation - and that this is the reason why some people lived with [infantile hypercalcemia type 1] but without a definitive diagnosis”, he added.
Off the back of this finding, the team hope to see how the shape and structure of genes may be implicated in other disorders such as cancer.
“On a wider scale relevant to genetics and health, we know that genes must have the correct sequence to produce the correct protein, but in an added layer of complexity, we now know that genes also have to have a correct physical shape,” continued Dr Green.
The new research was published in the Journal of Bone and Mineral Research.