ABSTRACT
OBJECTIVE: To characterize the clinical phenotype, genetic origin, and muscle pathology of patients with the FKRP c.1387A>G mutation. METHODS: Standardized clinical data were collected for all patients known to the authors with c.1387A>G mutations in FKRP. Muscle biopsies were reviewed and used for histopathology, immunostaining, Western blotting, and DNA extraction. Genetic analysis was performed on extracted DNA. RESULTS: We report the clinical phenotypes of 6 patients homozygous for the c.1387A>G mutation in FKRP. Onset of symptoms was <2 years, and 5 of the 6 patients never learned to walk. Brain MRIs were normal. Cognition was normal to mildly impaired. Microarray analysis of 5 homozygous FKRP c.1387A>G patients revealed a 500-kb region of shared homozygosity at 19q13.32, including FKRP. All 4 muscle biopsies available for review showed end-stage dystrophic pathology, near absence of glycosylated α-dystroglycan (α-DG) by immunofluorescence, and reduced molecular weight of α-DG compared with controls and patients with homozygous FKRP c.826C>A limb-girdle muscular dystrophy. CONCLUSIONS: The clinical features and muscle pathology in these newly reported patients homozygous for FKRP c.1387A>G confirm that this mutation causes congenital muscular dystrophy. The clinical severity might be explained by the greater reduction in α-DG glycosylation compared with that seen with the c.826C>A mutation. The shared region of homozygosity at 19q13.32 indicates that FKRP c.1387A>G is a founder mutation with an estimated age of 60 generations (â¼1,200-1,500 years).
ABSTRACT
A new species of Spigelia L. (Loganiaceae), Spigelia genuflexa Popovkin & Struwe, sp. n., from the Atlantic forest of northeastern Bahia, Brazil, is described, being the first reported geocarpic species in the family. During fruit maturation, the basal infructescences bend down towards the ground, depositing the fruit on the surface (and burying it in soft kinds of ground cover, e.g., moss), whereas the upper ones do so slightly but noticeably. The species is a short-lived annual apparently restricted to sandy-soil habitat of the Atlantic forest of northeastern Bahia, with variable and heterogeneous microenvironment and is known from only two restricted localities. A short review of amphi- and geocarpic species is provided. A discussion of comparative morphology within Spigelia with regards to dwarfism, indumentum, and annual habit is included. A phylogenetic parsimony and Bayesian analysis of ITS sequences from 15 Spigelia species plus 17 outgroups in Loganiaceae confirms its independent taxonomic status: on the basis of sequence similarity and phylogenetic topology it is phylogenetically distinct from all Spigelia species sequenced so far.
ABSTRACT
OBJECTIVE: To identify key factors for the delay in diagnosis of Duchenne muscular dystrophy (DMD) without known family history. STUDY DESIGN: The cohort comes from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet), a multistate, multiple-source, population-based surveillance system that identifies and gathers information on all cases of Duchenne and Becker muscular dystrophy born since 1982. We analyzed medical records of 453 Duchenne and Becker muscular dystrophy boys to document the time course and steps taken to reach a definitive diagnosis. RESULTS: Among 156 boys without known family history of DMD prior to birth, first signs or symptoms were noted at a mean age of 2.5 years. Concerns resulted in primary care provider evaluation of the child at a mean age of 3.6 years. Mean age at time of initial creatine kinase was 4.7 years. Mean age at definitive diagnosis of DMD was 4.9 years. CONCLUSIONS: There is a delay of about 2.5 years between onset of DMD symptoms and the time of definitive diagnosis, unchanged over the previous 2 decades. This delay results in lost opportunities for timely genetic counseling and initiation of corticosteroid treatment. We recommend checking creatine kinase early in the evaluation of boys with unexplained developmental delay.