Clinical characteristics and MTMR13/SBF2 gene mutation analysis of a Charcot - Marie-Tooth disease type 4B2 Chinese family

Abstract

Objective To explore the clinical features and genetic characteristics of Charcot-Marie-Tooth disease type 4B2 (CMT4B2) patients. Methods MTMR13/SBF2 gene mutations were screened by target region capture sequencing among a CMT4B2 Chinese family which included 3 patients. Results Case 1 (the proband) showed weakness in both lower limbs 6 years ago, running significantly slower than her classmates. The symptoms then became gradually worsened. Then the patient suffered from amyotrophy of thenar and hypothenar eminences and interosseus of her hands, bilateral finger joints could not be straightened, atrophy of bilateral leg muscles, talipes equinovarus appearance, and weakened tendon reflexes of limbs. Case 2 (the proband's younger brother) had weakness in both lower limbs and walked unsteadily 2 years ago, with running and going upstairs significantly slower than before. His abnormal walking gait got worsening in recent and he could not bend his feet upward in the stand or on the walk. He also presented amyotrophy of thenar and hypothenar eminences of his hands, mild atrophy of bilateral leg muscles, talipes equinovarus appearance, and weakened tendon reflex of limbs. Case 3 (the proband's another younger brother) also had difficulty in walking with the heel, and thenar and hypothenar eminences of his hands were mildly atrophic and the tendon reflexes were weakened. The result of proband's MTMR13/SBF2 gene test showed c.230G > A (p.Gln77Arg) and c.1537C > T (p.Gln513*) compound heterozygous mutations, her father carried c.230G > A (p.Gln77Arg) heterozygous mutation and her mother carried c.1537C > T (p.Gln513*) heterozygous mutation. Case 2 and Case 3 had the same compund heterozygous mutation as the proband. The 3 patients were diagnosed as CMT4B2, and their family was diagnosed as CMT4B2 pedigree. All patients were treated by mecobalamine. The proband was also treated by plaster immobilization to correct her talipes equinovarus. Conclusions CMT4B2 is a very rare and serious progressive type of CMT. Since there is no effective treatment of CMT4B2, we should carry out gene test as early as possible to make a clear diagnosis on patients and also take hereditary inquiry on the patient's family. For disease-causing gene carriers who want to have a baby, prenatal genetic diagnosis should be done to avoid the birth of CMT4B2 baby. For carriers of the gene without clinical symptoms or in early stage, close follow-up and active treatment should be taken to delay the onset and prevent talipes equinovarus or scoliosis, so as to improve the life quality of patients.

Keywords

• Charcot-Marie-Tooth disease
• Phenotype
• Genes
• Mutation
• Pedigree