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Abstract Objectives Cerebral palsy (CP) is the most common childhood motor disability, yet its link to single‐gene disorders is under‐characterized. To explore the genetic landscape of CP, we conducted whole exome sequencing (WES) in a cohort of patients with CP. Methods We performed comprehensive phenotyping and WES on a prospective cohort of individuals with cryptogenic CP (who meet criteria for CP; have no risk factors), non‐cryptogenic CP (who meet criteria for CP; have at least one risk factor), and CP masqueraders (who could be diagnosed with CP, but have regression/progressive symptoms). We characterized motor phenotypes, ascertained medical comorbidities, and classified brain MRIs. We analyzed WES data using an institutional pipeline. Results We included 50 probands in this analysis (20 females, 30 males). Twenty‐four had cryptogenic CP, 20 had non‐cryptogenic CP, five had CP masquerader classification, and one had unknown classification. Hypotonic‐ataxic subtype showed a difference in prevalence across the classification groups (p = 0.01). Twenty‐six percent of participants (13/50) had a pathogenic/likely pathogenic variant in 13 unique genes (ECHS1, SATB2, ZMYM2, ADAT3, COL4A1, THOC2, SLC16A2, SPAST, POLR2A, GNAO1, PDHX, ACADM, ATL1), including one patient with two genetic disorders (ACADM, PDHX) and two patients with a SPAST‐related disorder. The CP masquerader category had the highest diagnostic yield (n = 3/5, 60%), followed by the cryptogenic CP category (n = 7/24, 29%). Fifteen percent of patients with non‐cryptogenic CP (n = 3/20) had a Mendelian disorder on WES. Interpretation WES demonstrated a significant prevalence of Mendelian disorders in individuals clinically diagnosed with CP, including in individuals with known CP risk factors.

Background: Most knee surgeons have believed during TKA neutral mechanical alignment should be restored. A number of patients may exist, however, for whom neutral mechanical alignment is abnormal. Patients with so-called "constitutional varus" knees have had varus alignment since they reached skeletal maturity. Restoring neutral alignment in these cases may in fact be abnormal and undesirable and would likely require some degree of medial soft tissue release to achieve neutral alignment.Questions/purposes: We investigated what percentage of the normal population has constitutional varus knees and what are the contributing factors.Subjects and Methods: We recruited a cohort of 250 asymptomatic adult volunteers between 20 and 27 years old for this cross-sectional study. All volunteers had full-leg standing digital radiographs on which 19 alignment parameters were analyzed. The incidence of constitutional varus alignment was determined and contributing factors were analyzed using multivariate prediction models.Results: Thirty-two percent of men and 17% of women had constitutional varus knees with a natural mechanical alignment of 3° varus or more. Constitutional varus was associated with increased sports activity during growth, increased femoral varus bowing, an increased varus femoral neck-shaft angle, and an increased femoral anatomic mechanical angle.Conclusions: An important fraction of the normal population has a natural alignment at the end of growth of 3° varus or more. This might be a consequence of Hueter-Volkmann's law. Restoration of mechanical alignment to neutral in these cases may not be desirable and would be unnatural for them. [ABSTRACT FROM AUTHOR]

BackgroundRecent studies have sought to describe HIV infection and transmission characteristics around the world. Identification of early HIV-1 infection is essential to proper surveillance and description of regional transmission trends. In this study we compare people recently infected (RI) with HIV-1, as defined by Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS), to those with chronic infection.Methodology/principal findingsSubjects were identified from 2002-2004 at four testing sites in São Paulo. Of 485 HIV-1-positive subjects, 57 (12%) were defined as RI. Of the participants, 165 (34.0%) were aware of their serostatus at the time of HIV-1 testing. This proportion was statistically larger (p59 years-old age strata (pConclusions/significanceIn this study, we evaluated RI individuals and discovered that HIV-1 has been spreading among younger individuals in São Paulo and preventive approaches should, therefore, target this age stratum.