Chronic atrial and intestinal dysrhythmia – SGOL1 gene 

            Chronic Atrial and Intestinal Dysrhythmia (CAID) is a disease that affects the heart and the digestive system. This disease alters the normal rhythm of the heartbeat, leading to an abnormality of the heart rhythm called sick sinus syndrome, and affects the rhythmic muscle contractions that drive food through the intestine (peristalsis), leading to an alteration called intestinal pseudo-obstruction. Cardiac and digestive problems develop at the same time, usually at 20 years of age.

Sick sinus syndrome (also known as sinus node dysfunction) is an anomaly of the sinoatrial node (SA node). The SA node generates electrical impulses that begin every heartbeat. In people with sick sinus syndrome, the SA node does not function normally, which usually causes bradycardia, tachycardia or tachycardia-bradycardia syndrome. Symptoms related to abnormal heartbeats may include dizziness, lightheadedness, syncope, palpitations and confusion or memory problems. During exercise, many affected people have chest pain, shortness of breath or tiredness.

On the other hand, intestinal pseudo-obstruction leads to an accumulation of partially digested food in the intestine. This accumulation can cause bloating and pain, nausea, vomiting and constipation or diarrhea. Affected people have loss of appetite and impaired ability to absorb nutrients, which can lead to malnutrition. These symptoms resemble those of an intestinal obstruction, but no intestinal blockage occurs in the intestinal pseudo-obstruction.

Chronic Atrial and Intestinal Dysrhythmia (CAID) is due to changes in the SGOL1 gene, located on the short arm of chromosome 3 (3p24.3). This gene encodes part of a protein complex called cohesin. This protein complex helps control the placement of chromosomes during cell division. Before cells divide, all their chromosomes must be copied. The DNA copied from each chromosome is arranged in two identical structures, the sister chromatids, which are attached to each other throughout the early stages of cell division. In this process, cohesin keeps the sister chromatids together and, in doing so, helps maintain the stability of the chromosomal structure during cell division.

At least one mutation of the SGOL1 gene has been identified in people with Chronic Atrial and Digestive Dysrhythmia (CAID). The associated mutation replaces the amino acid lysine with the amino acid glutamic acid at position 23 of the protein (Lys23Glu or K23E). It is likely that this change may result in a cohesin complex that is less able to hold sister chromatids together, leading to a decrease in chromosomal stability during cell division. It is believed that this instability causes the senescence of the cells in the intestinal muscle and in the sinus node, leading to maintenance problems of the rhythmic movements of the heart and intestines and, which leads to the signs and symptoms of CAID. Although it is not clear why SGOL1 genetic mutations specifically affect the heart and intestines in CAID, it is likely that the expression of the SGOL1 gene in certain embryonic tissues or a particular function of the SGOL1 protein in the sinoatrial node and in cells that help control the rhythm of bowel movements, can respond to the characteristics of the disease.

This disease is inherited with an autosomal recessive pattern, that is, both copies of the gene in each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with Chronic atrial and intestinal dysrhythmia syndrome (CAID), by means of the complete PCR amplification of the exons of the SGOL1 gene, respectively, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).