ABSTRACT
OBJECTIVE: To study the histopathological characteristics and mutation spectrum of patients presenting with the Duchenne muscular dystrophy (DMD) phenotype. METHODS: This was a descriptive study conducted over a period of 8 years. Multiplex ligation-dependent probe amplification (MLPA) was done in patients presenting with the DMD phenotype. If MLPA was negative, patients were offered muscle biopsy for histopathological studies and/or next generation sequencing (NGS) based multigene panel testing for muscular dystrophies. RESULTS: Of the 510 patients included, mutation in the DMD gene was detected by MLPA in 372 (72.9%), of whom 342 (67.1%) had exonic deletions and 30 (5.9%) had exonic duplications. Exons 45-55 were most commonly involved in large deletions and exons 1-10 were the commonest exons involved in duplications. In the MLPA-negative cohort, 27 proceeded for muscle biopsy. NGS was done in 14 patients, 10 of whom had pathogenic mutations in the DMD gene, 3 were non dystrophinopathies and no pathogenic variant could be identified in one patient. CONCLUSIONS: For patients presenting with the DMD phenotype, MLPA of the DMD gene has a high diagnostic rate of about 73%, and non-dystrophinopathies may constitute a small but significant proportion.
Subject(s)
Biopsy/methods , Dystrophin/genetics , Genetic Testing , Muscular Dystrophy, Duchenne , Adolescent , Age of Onset , Child , Child, Preschool , Genetic Testing/methods , Genetic Testing/statistics & numerical data , Humans , Immunohistochemistry , India/epidemiology , Male , Medical History Taking/methods , Motor Skills Disorders/diagnosis , Motor Skills Disorders/epidemiology , Multiplex Polymerase Chain Reaction/methods , Muscular Dystrophy, Duchenne/diagnosis , Muscular Dystrophy, Duchenne/epidemiology , Muscular Dystrophy, Duchenne/genetics , Muscular Dystrophy, Duchenne/physiopathology , Mutation , Symptom Assessment/methods , Tertiary Care Centers/statistics & numerical dataABSTRACT
While knowledge of HBB gene mutations is necessary for offering prenatal diagnosis (PND) of ß-thalassemia (ß-thal), a genotype-phenotype correlation may not always be available for rare variants. We present for the first time, genotype-phenotype correlation for a compound heterozygous status with IVS-I-5 (G>C) (HBB: c.92+5G>C) and HBB: c.407C>T (Hb Alperton) mutations on the HBB gene in an Indian family. Hb Alperton is a very rare hemoglobin (Hb) variant with scant published information about its clinical presentation, especially when accompanied with another HBB gene mutation. Here we provide biochemical as well as clinical details of this variant.
