Classification, nosology and diagnostics of Ehlers-Danlos syndrome

Ehlers-Danlos syndrome (EDS) comprises a group of heritable connective tissue disorders which has as cardinal features varying degrees of skin hyperextensibility, joint hypermobility, easy bruising and skin fragility. The 2017 New York nosology distinguishes 13 types of EDS, which all, except hypermobile EDS, have a known molecular basis. Hypermobile EDS is recognized as a common and often disabling disorder, incorporating benign joint hypermobility syndrome. EDS needs to be differentiated from other connective tissue disorders, in particular Marfan syndrome, Loeys-Dietz syndrome and cutis laxa. The frequent types of EDS can be diagnosed after careful history taking and clinical examination, but for definite diagnosis molecular confirmation is needed in all types. Management for EDS patients preferably is provided by multidisciplinary teams in expertise centres. After diagnosing EDS genetic counselling is an essential part of the management of patients and their family

XLMR genes: update 2000

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Holt-Oram Syndrome; A Case report

Holt-Oram syndrome is a rare genetic autosomal dominant disorder which affects the preaxial radial ray of the upper limbs and septation of the heart and/or cardiac conduction. The present article describes the clinical and radiological features of Holt–Oram syndrome in a Tanzanian patient. This case emphasises the importance of proper prenatal screening for congenital anomalies and counselling of the parents.   &nbsp

Paroxysmal Kinesigenic Dyskinesia: First Molecularly Confirmed Case from Africa

Background: Paroxysmal kinesigenic dyskinesia (PKD) is a movement disorder, with an excellent response to carbamazepine treatment. It has been described in various populations, but not yet in an African population. Case report: In a patient who reported to clinic with side effects of carbamazepine, PRRT2 gene screening was performed based on a clinical history compatible with PKD. A common PRRT2 mutation was identified in this patient, hereby the first genetically confirmed PRRT2-associated PKD in Africa. Discussion: Reporting genetic confirmation of an unusual movement disorder from an equally unusual location shows the wide geographical distribution of PRRT2-associated disease. It also illustrates recognizability of this treatable disorder where the easiest accessible diagnostic tool is neurological history and examination

Schur Polynomials and the Yang-Baxter equation

We show that within the six-vertex model there is a parametrized Yang-Baxter equation with nonabelian parameter group GL(2)xGL(1) at the center of the disordered regime. As an application we rederive deformations of the Weyl character formule of Tokuyama and of Hamel and King.Comment: Revised introduction; slightly changed reference

Novel likely pathogenic variant in NR5A1 gene in a Tanzanian child with 46,XY differences of sex development, inherited from the mosaic father

Pathogenic variants in the nuclear receptor subfamily 5 group A member 1 gene (NR5A1), which encodes steroidogenic factor 1 (SF1), result in 46,XY and 46,XX differences of sex development (DSD). In 46,XY individuals with a pathogenic variant in the NR5A1 gene a variable phenotype ranging from mild to severe is seen, including adrenal failure, testis dysgenesis, androgen synthesis defects, hypospadias and anorchia with microphallus and infertility. We report the clinical, endocrinological and genetic characteristics of a patient with 46,XY DSD with a novel likely pathogenic missense variant in the NR5A1 gene. A retrospective evaluation of the medical history, physical examination, limited endocrinological laboratory analysis and genetic analysis with DSD gene panel testing was performed. A 1.5-month-old individual was referred with ambiguous genitalia. The karyotype was 46,XY. The endocrinological analyses were within normal male reference including a normal response of cortisol within an adrenocorticotropic hormone test. A novel heterozygous missense variant c.206G&gt;C p.(Arg69Pro) in the NR5A1 gene was detected. This variant was present in mosaic form (~20%) in his unaffected father. Because another missense variant at the same position and other missense variants involving the same highly conserved codon have been reported, we consider this NR5A1 variant in this 46,XY DSD patient as likely pathogenic in accordance with the ACMG/AMP 2015 guidelines causing ambiguous genitalia but no adrenal insufficiency. This variant was inherited from the apparently unaffected mosaic father, which might have implications for the recurrence risk in this family.Learning pointsThe importance of performing trio (patient and parents) sequencing is crucial in pointing out the origin of inheritance.In a 46,XY differences of sex development patient, a normal adrenal function does not rule out an NR5A1 mutation.With the support of a dedicated overseas institute partnership, we could solve this complex clinical case by molecular diagnosis in a resource-limited setting.</p

Crystal constructions in Number Theory

Weyl group multiple Dirichlet series and metaplectic Whittaker functions can be described in terms of crystal graphs. We present crystals as parameterized by Littelmann patterns and we give a survey of purely combinatorial constructions of prime power coefficients of Weyl group multiple Dirichlet series and metaplectic Whittaker functions using the language of crystal graphs. We explore how the branching structure of crystals manifests in these constructions, and how it allows access to some intricate objects in number theory and related open questions using tools of algebraic combinatorics

Uniparental disomy 7 in Silver—Russell syndrome and primordial growth retardation

Maternal uniparental disomy for the entire chromosome 7 has so far been reported in three patients with intrauterine and postnatal growth retardation. Two were detected because they were homozygous for a cystic fibrosis mutation for which only the mother was heterozygous, and one because he was homozygous for a rare COL1A2 mutation. We investigated 35 patients with either the Silver-Russell syndrome or primordial growth retardation and their parents with PCR markers to search for uniparental disomy 7. Four of 35 patients were found to have maternal disomy, including three with isodisomy and one with heterodisomy. The data confirm the hypothetical localization of a maternally imprinted gene (or more than one such gene) on chromosome 7. It is suggested to search for UPD 7 in families with an offspring with sporadic Silver-Russell syndrome or primordial growth retardatio