SPTLC2 gene mutation leads to intermediate Charcot-Marries-Tooth disease: a family report / 中华神经科杂志

Objective:To report a SPTLC2 gene mutation in a family with a phenotype of Charcot-Marie-Tooth disease.Methods:To screen the family of patients with pathogenic mutations of SPTLC2 gene from the database of hereditary peripheral neuropathy in the Department of Neurology, Peking University First Hospital, and to collect their clinical data, peripheral nerve conduction examination, nerve ultrasound examination, pathological examination of the peroneal nerve and whole exome sequencing results of prohand.Results:One family was screened, the proband was a 16-year-old female with 4 years of sensory loss and anhidrosis of both lower limbs and 16 months of walking difficulty who admitted to Peking University First Hospital in January 2022. Physical examination showed sensory loss, dry skin and weakness in distal limbs. Her father had numbness and dry skin in the distal lower limbs from childhood,weakness and atrophy of his lower limbs in adulthood. He died at age of 52 years old. The nerve conduction study revealed no action potentials of the sensory and motor nerves of the lower limbs in the proband. The amplitude of the compound muscle action potential of the motor conduction of the bilateral ulnar nerve and median nerve decreased, and the nerve conduction velocity of the bilateral median nerve were 32 m/s and 24 m/s. Neurosonography showed thickening of peripheral nerves. Sural biopsy revealed severe loss of myelinated and unmyelinated nerve fibers with onion bulbs formation. SPTLC2 gene showed a known heterozygous p.G435V mutation. The lower limb weakness was improved after oral L-serine.Conclusions:SPTLC2 gene mutation can lead to an intermediate Charcot-Marie-Tooth disease phenotype. L-serine can improve the limb weakness.

A Study on Altered Expression of Serine Palmitoyltransferase and Ceramidase in Psoriatic Skin Lesion

Ceramides are the main lipid component maintaining the lamellae structure of stratum corneum, as well as lipid second messengers for the regulation of cellular proliferation and/or apoptosis. In our previous study, psoriatic skin lesions showed marked decreased levels of ceramides and signaling molecules, specially protein kinase C-alpha (PKC-alpha) and c-jun N-terminal kinase (JNK) in proportion to the psoriasis area and severity index (PASI) scores, which suggested that the depletion of ceramide is responsible for epidermal hyperproliferation of psoriasis via downregulation of proapoptotic signal cascade such as PKC-alpha and JNK. In this study, we investigated the protein expression of serine palmitoyltransferase (SPT) and ceramidase, two major ceramide metabolizing enzymes, in both psoriatic epidermis and non-lesional epidermis. The expression of SPT, the ceramide generating enzyme in the de novo synthesis in psoriatic epidermis, was significantly less than that of the non-lesional epidermis, which was inversely correlated with PASI score. However, the expression of ceramidase, the degradative enzyme of ceramides, showed no significant difference between the lesional epidermis and the non-lesional epidermis of psoriatic patients. This might suggest that decreased expression of SPT protein is one of the important causative factors for decreased ceramide levels in psoriasis.