RESUMO
This article reports a case of limb-girdle muscular dystrophy type 1B (LGMD1B) caused by a novel splicing heterozygous mutation in the LMNA gene. The proband presented with progressive aggravation of weakness in walking. There was no atrophy of the scapular muscles and the lower-extremity proximal muscles, with normal muscle tension of the extremities, grade 4 muscle strength in the upper and lower extremities, and positive Gower sign. The level of creatine kinase was 779 U/L. Muscle hematoxylin-eosin staining showed muscular dystrophy, and there was no significant reduction in the expression of Lamin A protein. Second-generation sequencing revealed a novel splicing heterozygous mutation, c.810+2T>C, in the LMNA gene, while this locus was normal in his parents. GERP++RS software predicted that the mutation site was highly conservative. Human Splice Finder and Spliceman software predicted that the mutation might be a pathogenic mutation. ExPASy software predicted that the new amino acid sequence became shorter. There were two sequences of mRNA in the patient's muscle: one was the normal sequence, which accounted for 92.2%; the other was partial intron 4 retention, which was the abnormal splice variant accounting for 7.8%. LGMD1B is a type of autosomal dominant inherited myopathy caused by a mutation in the LMNA gene located on the autosomal 1q22. This study extends the mutation spectrum of the LMNA gene and provides help to the diagnosis of LGMD1B.
Assuntos
Humanos , Sequência de Aminoácidos , Lamina Tipo A , Distrofia Muscular do Cíngulo dos Membros , MutaçãoRESUMO
This article reported the clinical features of one child with infantile hypophosphatasia (HPP) and his pedigree information. The proband was a 5-month-old boy with multiple skeletal dysplasia (koilosternia, bending deformity of both radii, and knock-knee deformity of both knees), feeding difficulty, reduction in body weight, developmental delay, recurrent pneumonia and respiratory failure, and a significant reduction in blood alkaline phosphatase. Among his parents, sister, uncle, and aunt (other family members did not cooperate with us in the examination), his parents and aunt had a slight reduction in alkaline phosphatase and his aunt had scoliosis; there were no other clinical phenotypes or abnormal laboratory testing results. His ALPL gene mutation came from c.228delG mutation in his mother and c.407G>A compound heterozygous mutation in his father. His aunt carried c.228delG mutation. The c.407G>A mutation had been reported as the pathogenic mutation of HPP, and c.228delG mutation was a novel pathogenic mutation. Hypophosphatasia is caused by ALPL gene mutation, and ALPL gene detection is an effective diagnostic method. This study expands the mutation spectrum of ALPL gene and provides a theoretical basis for genetic diagnosis of this disease.