Yuan-Harel-Lupski syndrome - PMP22 and RAI1 genes, and Chromosome 17

The Yuan-Harel-Lupski syndrome (YUHAL) is a rare neurological disorder that presents a combination of characteristics of two other processes, namely Potocki-Lupski syndrome and Charcot-Marie-Tooth disease type 1A.

The first signs and symptoms of YUHAL syndrome begin in childhood, and include hypotonia, delay in the development of motor and language skills, behavioral disorders, sleep difficulties and/or sleep apnea. In addition, individuals with YUHAL syndrome may manifest subtle differences in facial features, including downward sloping palpebral fissures, a triangular face and strabismus. Other signs and symptoms begin in childhood as a result of peripheral nerve damage, which can lead to atrophy of the leg muscles and muscle weakness. Some affected people have abnormalities in the feet, such as flat feet, high arch of the foot, or clubfoot. In addition, cases of individuals with abnormal development of other tissues and organs, such as the heart or kidneys, have been described, as well as a decrease in reflexes and sensitivity to touch, heat and cold in the feet, and in the lower legs.

This process is due to a duplication that occurs in the short arm of chromosome 17 in the region 17p12-17p11.2. The duplicated segment varies in size from approximately 3.2 Mb to 19.7 Mb. The duplicated region always contains at least two genes: the RAI1 (retinoic acid induced 1) and the PMP22 (peripheral myelin protein 22). It is believed that having an additional copy of other genes in the duplicated region contributes to other features of the disease, such as kidney abnormalities.

The RAI1 gene, located on the short arm of chromosome 17 (17p11.2), encodes a protein that helps regulate the expression of certain genes, such as those involved in circadian rhythms. The RAI1 protein also seems to play a role in the development of the brain and craniofacial bones. It is believed that having an additional copy of the RAI1 gene in each cell underlies many of the main features of YUHAL syndrome, such as late development, behavioral problems and some other associated characteristic abnormalities.

The PMP22 gene, located on the short arm of chromosome 17 (17p12), encodes peripheral myelin protein 22 (PMP22). This protein is found in the peripheral nervous system and is a component of myelin. It is produced primarily by Schwann cells, which wrap and insulate nerves. Inside Schwann cells, PMP22 protein plays a crucial role in the development and maintenance of myelin. Studies suggest that PMP22 protein is particularly important for protecting nerves from physical pressure, helping them restore their structure after being compressed. The PMP22 gene also plays a role in the growth of Schwann cells and in the process of cell differentiation. It is believed that having an additional copy of the PMP22 gene results in nerve disorders that cause abnormalities in the lower legs and feet.

The YUHAL syndrome is inherited with an autosomal dominant pattern, which means that a copy of the duplication of chromosomes in each cell is sufficient to express the process. Most cases of the disease are due to new mutations that occur during the formation of reproductive cells or early embryonic development. These cases occur in people with no history of the disease in their family.

Tests performed in IVAMI: in IVAMI we perform the detection of deletions in chromosome 17 associated with the Yuan-Harel-Lupski syndrome, by means of the PCR quantification at real time.

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).