Like other rare disorders, CTNNB1 Syndrome isn’t definitively diagnosed until a complete genetic test has been performed and confirms the mutation or deletion of the CTNNB1 gene. To help explain the terminology we use to describe CTNNB1 Syndrome and CTNNB1 research, we’ve compiled introductory information about genetics and genetic testing.

Genetics 101

  • A gene is the basic physical and functional unit of heredity. Genes are made up of DNA. Some genes act as instructions to make molecules called proteins. However, many genes do not code for proteins. In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases. The Human Genome Project estimated that humans have between 20,000 and 25,000 genes. 
  • Every person has two copies of each gene, one inherited from each parent. Most genes are the same in all people, but a small number of genes (less than 1 percent of the total) are slightly different between people. Alleles are forms of the same gene with small differences in their sequence of DNA bases. These small differences contribute to each person’s unique physical features.
  • Scientists keep track of genes by giving them unique names. Because gene names can be long, genes are also assigned symbols, which are short combinations of letters (and sometimes numbers) that represent an abbreviated version of the gene name.
  • For example, CTNNB1 is a gene on chromosome 3 that has been associated with production of a protein called beta catenin.

Source: National Institute of Health

  • Most genes contain the information needed to make functional molecules called proteins. (A few genes produce other molecules that help the cell assemble proteins.) The journey from gene to protein is complex and tightly controlled within each cell. It consists of two major steps: transcription and translation. Together, transcription and translation are known as gene expression. 
  • During the process of transcription, the information stored in a gene’s DNA is transferred to a similar molecule called RNA (ribonucleic acid) in the cell nucleus. Both RNA and DNA are made up of a chain of nucleotide bases, but they have slightly different chemical properties. The type of RNA that contains the information for making a protein is called messenger RNA (mRNA) because it carries the information, or message, from the DNA out of the nucleus into the cytoplasm.
  • Translation, the second step in getting from a gene to a protein, takes place in the cytoplasm. The mRNA interacts with a specialized complex called a ribosome, which “reads” the sequence of mRNA bases. Each sequence of three bases, called a codon, usually codes for one particular amino acid. (Amino acids are the building blocks of proteins.) A type of RNA called transfer RNA (tRNA) assembles the protein, one amino acid at a time. Protein assembly continues until the ribosome encounters a “stop” codon (a sequence of three bases that does not code for an amino acid).

Source: National Institute of Health

  • DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA). Mitochondria are structures within cells that convert the energy from food into a form that cells can use.
  • The information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of about 3 billion bases, and more than 99 percent of those bases are the same in all people. The order, or sequence, of these bases determines the information available for building and maintaining an organism, similar to the way in which letters of the alphabet appear in a certain order to form words and sentences.
  • DNA bases pair up with each other, A with T and C with G, to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. Together, a base, sugar, and phosphate are called a nucleotide. Nucleotides are arranged in two long strands that form a spiral called a double helix. The structure of the double helix is somewhat like a ladder, with the base pairs forming the ladder’s rungs and the sugar and phosphate molecules forming the vertical sidepieces of the ladder.
  • An important property of DNA is that it can replicate, or make copies of itself. Each strand of DNA in the double helix can serve as a pattern for duplicating the sequence of bases. This is critical when cells divide because each new cell needs to have an exact copy of the DNA present in the old cell.

Source: National Institute of Health

  • A biological pathway is a series of actions among molecules in a cell that leads to a certain product or a change in the cell. It can trigger the assembly of new molecules, such as a fat or protein, turn genes on and off, or spur a cell to move.
  • For your body to develop properly and stay healthy, many things must work together at many different levels – from organs to cells to genes.
  • From both inside and outside the body, cells are constantly receiving chemical cues prompted by such things as injury, infection, stress or even the presence or lack of food. To react and adjust to these cues, cells send and receive signals through biological pathways. The molecules that make up biological pathways interact with signals, as well as with each other, to carry out their designated tasks.
  • Biological pathways can act over short or long distances. For example, some cells send signals to nearby cells to repair localized damage, such as a scratch on a knee. Other cells produce substances, such as hormones, that travel through the blood to distant target cells.
  • These biological pathways control a person’s response to the world. For example, some pathways subtly affect how the body processes drugs, while others play a major role in how a fertilized egg develops into a baby. Other pathways maintain balance while a person is walking, control how and when the pupil in the eye opens or closes in response to light, and affect the skin’s reaction to changing temperature.
  • Regulation of the Wnt signaling pathway is a finely tuned balancing act aimed toward cellular differentiation and the maintenance of tissue homeostasis.

Genetic Testing for CTNNB1 Syndrome

Because there is a wide range of development, behavioral and physical characteristics associated with CTNNB1 Syndrome, genetic testing is an essential step to receiving a correct diagnosis. Today, CTNNB1 Syndrome is definitively diagnosed using Whole Exome Sequencing (WES). 

This type of comprehensive analysis takes a deep dive into more genes than standard genetic tests and is commonly used to help find the genetic mutations causing a patient’s symptoms. It uses DNA samples from parents and the child, which helps determine if a genetic mutation is a random (de novo) occurrence. Learn more about Whole Exome Sequencing and its uses in the family guide from Cincinnati Children’s Hospital.

As a result of better diagnostic capabilities through genetic testing, the number of CTNNB1 patients has increased from a handful of individuals to an estimated 300 youth and adult patients worldwide. Get to know our community, their stories of diagnosis and beyond.