ABSTRACT
Objective To analyze the clinical characteristics,muscle pathological features and pathogenic gene mutation in 4 cases with LMNA-related congenital muscular dystrophy (L-CMD).Methods Clinical data of the probands and the parents were collected.Skeletal muscle specimens were biopsied from the probands for pathological analysis.Genomic DNA and RNA were extracted from peripheral blood leukocytes,and PCR,reverse transcription(RT)-PCR and DNA direct sequencing were employed to analyze the LMNA gene to determine the gene mutation and confirm the pathogenicity.Results Four patients had symptoms from fetal period to several months after birth.They presented with motor retardation,muscle weakness with prominent the proximal upper limbs,distal lower limbs and neck extensor,hypotonia,contractures,with mild to moderate elevation of CK level.The muscle biopsies showed muscular dystrophic and with inflammatory changes,and the abnormal nuclear morphology was observed with transmission electron microscopy.Genetic analysis of them detected 4 dominant de novo mutations.Three of them had unreported pathogenic mutations.The same sites of the LMNA gene were wild type in their parents.Conclusions Four cases of L-CMD are genetically identified.Genetic counseling of the family can be possible.The patients should be considered LMNA gene mutation of they present themselves with muscle weakness with the proximal upper limbs,distal lower limbs and neck extensor,hypotonia,contractures,mild to moderate elevation of CK level,and if the biopsies show muscular dystrophic changes but also with inflammatory changes should be considered LMNA gene mutation.Genetic analysis is the most reliable method for diagnosing L-CMD.
ABSTRACT
<p><b>OBJECTIVE</b>To study the clinical feature of a Chinese family with muscle-eye-brain disease (MEB) and the mutation of protein O-linked-mannose beta-1, 2-N-acetylglucosaminyltransferase 1 gene (POMGNT1).</p><p><b>METHODS</b>Clinical data of the proband and his family members were collected. Genomic DNA from the patient and his parents was extracted using standard procedures from the peripheral blood leukocytes. Polymerase chain reaction and DNA direct sequencing were employed to analyze all of the exons to determine the mutation, and the relationship between genotype and phenotype was analyzed.</p><p><b>RESULTS</b>The proband was diagnosed as floppy baby, presented with delayed psychomotor development and myopathic face. His serum creatine kinase (CK) level elevated moderately and brain MRI showed cerebral and cerebellar gyrus abnormalities with white matter signal intensity changes, cerebellar cysts and cerebellar and brain stem hypoplasia, consistent with congenital muscular dystrophy with eye brain disorder. Further test with DNA detected a compound heterozygous mutation of c.1896 1 G to C before exon 22 which may induce splicing error, and missense mutation c.1319T to G, p.L440R in exon 16. Both parents had a heterozygous mutation at the mutation sites.</p><p><b>CONCLUSION</b>According to our study, the family is diagnosed as MEB. The proband carried compound heterozygous mutations in the POMGNT1 gene, and his parents are heterozygous carriers, which is consistent with autosomal recessive inheritance. The child is definitely diagnosed as having muscle eye brain disease.</p>