Phenotypic and Genotypic Analysis of RETT Syndrome

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Hemizygous nonsense variant in the moesin gene (MSN) leads to a new autoimmune phenotype of Immunodeficiency 50

Here we describe the investigation of two male siblings with juvenile total loss of teeth, early onset chronic leg ulcers and autoimmune thyroiditis in both patients, as well as focal segmental glomerulosclerosis with associated pulmonal emphysema in one and diabetes mellitus in the other patient. The clinical picture and lupus anticoagulant, cryoglobulin and cold agglutinin positivity suggested the diagnosis of antiphospholipid syndrome. Flow cytometry analysis showed immunophenotypes consistent with immune dysregulation: low number of naive T cells, elevated CD4+ T cell counts and decreased CD8+ T cell counts were detected, and more than half of the T helper population was activated. Because of the siblings’ almost identical clinical phenotype genetic alteration was suspected in the background of the immunodeficiency. Whole exome sequencing identified a previously not described hemizygous nonsense variant (c.650G>A, p.W217X) within exon 6 of the moesin gene (MSN) localized on chromosome X, resulting in significantly decreased MSN mRNA expression compared to healthy controls. We present a putative new autoimmune phenotype of Immunodeficiency 50 (MIM300988) characterized by antiphospholipid syndrome, Hashimoto’s thyroiditis, leg ulcer and juvenile loss of teeth, associated with W217X mutation of the MSN gene

Clinical and genetic heterogeneity in frontometaphyseal dysplasia: Severe progressive scoliosis in two families

info:eu-repo/semantics/publishe

Clinical And Genetic Heterogeneity In Frontometaphyseal Dysplasia; Severe Progressive Scoliosis In Two Families

info:eu-repo/semantics/publishe

Cleidocranial dysplasia with decreased bone density and biochemical findings of hypophosphatasia

Cleidocranial dysplasia (CCD; MIM 119600) is an autosomal dominant skeletal dysplasia characterised by hypoplastic clavicles, patent fontanelles, short stature, tooth anomalies and other variable skeletal changes. Different mutations of the RUNX2/CBFA1 gene (MIM 600211) have been detected in patients with CCD. We investigated a mother and daughter with features of CCD presenting with reduced plasma alkaline phosphatase activity, increased urinary phosphoethanolamine excretion and decreased bone density. The latter findings were suggestive of hypophophatasia but mutation analysis showed no mutation in the tissue-nonspecific alkaline phosphatase gene (TNSALP; MIM 171760). However, a heterozygous mutation (Arg169Pro caused by nucleotide change 506G > C) was detected in the RUNX2 gene. Metabolic alterations gradually improved in both mother and daughter but bone-specific alkaline phosphatase remained low (less than 30% of normal) and mild phosphoethanolaminuria persisted. Recent studies in the Cbfa1 knock-out mouse showed decreased expression of alkaline phosphatase in differentiating bone.status: publishe

Cleidocranial dysplasia with decreased bone density and biochemical findings of hypophosphatasia

Abstract. Cleidocranial dysplasia (CCD; MIM 119600) is an autosomal dominant skeletal dysplasia characterised by hypoplastic clavicles, patent fontanelles, short stature, tooth anomalies and other variable skeletal changes. Different mutations of the RUNX2/CBFA1 gene (MIM 600211) have been detected in patients with CCD. We investigated a mother and daughter with features of CCD presenting with reduced plasma alkaline phosphatase activity, increased urinary phosphoethanolamine excretion and decreased bone density. The latter findings were suggestive of hypophophatasia but mutation analysis showed no mutation in the tissue-nonspecific alkaline phosphatase gene (TNSALP; MIM 171760). However, a heterozygous mutation (Arg169Pro caused by nucleotide change 506G>C) was detected in the RUNX2 gene. Metabolic alterations gradually improved in both mother and daughter but bone-specific alkaline phosphatase remained low (less than 30% of normal) and mild phosphoethanolaminuria persisted. Recent studies in the Cbfa1 knock-out mouse showed decreased expression of alkaline phosphatase in differentiating bone. Conclusion: we suggest that the observed metabolic alterations are secondary to the RUNX2 gene mutation affecting early bone maturation and turnover. This is the first description of biochemical findings of hypophosphatasia in patients with cleidocranial dysplasia

Mutation analysis of MECP2 and determination of the X-inactivation pattern in Hungarian Rett syndrome patients

status: publishe

A Huntington-betegség preszimptómás genetikai vizsgálatát kérők pszichológiai felkészítése = Psychological aspects of presymptomatic diagnosis in Huntington disease

A Huntington-betegség autoszomális domináns módon öröklődő, felnőttkorban kezdődő, progresszív lefolyású, neurodegeneratív kórkép. Preszimptómás tesztelésére (genetikai vizsgálat elvégzésére a tünetek megjelenése előtt) nemzetközi ajánlásokat dolgoztak ki. A tesztelés előtti felkészítő folyamatban genetikus, neurológus, pszichológus vesz részt. Célkitűzés: A szerzők azt vizsgálták, hogy a nemzetközi ajánlások az általuk vizsgált tíz esetben mindig követhetők voltak-e, illetve mennyire kellett személyre szabottan végezni a felkészítést. Módszer: A szerzők az irodalmi adatokra támaszkodva protokollt dolgoztak ki a tájékoztatáson alapuló döntéshozatal elősegítésére, amelyben fontos része van a pszichológiai felkészítésnek. Tíz olyan személy esetét mutatják be, akik a családban előforduló Huntington-betegség miatt kérték a preszimptómás vizsgálatot. Eredmények: A vizsgálatot kérő tíz személy közül négyen a pszichológiai felkészítés elvégzése után, két személy már a felkészítés befejezése előtt kérte a genetikai vizsgálat elvégzését. Négy személy a pszichológiai felkészítés során elállt eredeti szándékától. Következtetések: A protokoll lépéseinek követése mellett egyéni tényezőket is figyelembe kell venni a személyre szabott preszimptómás tesztelés során. Az irodalmi ajánlások kiegészítéseként a szerzők javasolják a genetikai teszt elkészülte utáni kapcsolattartást is. | Introduction: Huntington disease is an autosomal dominant, progressive neurodegenerative disorder, starting in adulthood. International recommendations were created for presymptomatic testing (genetic test performed before symptoms appear). During the initial preparation for presymptomatic testing, a genetic counsellor, neurologist and psychologist attend. Aim: The authors evaluated whether the international recommendations could be used in the 10 cases examined, and how much the process must be individualized. Method: The authors stated a protocol based on the literature, and utilized it for the purpose of obtaining informed consent. Psychological preparation was an important part of this process. Ten cases are presented in whose families Huntington disease was determined, and therefore they asked for their own presymptomatic testing. Results: From the ten persons who asked for examination, four changed their minds during the psychological process; four were attended in the process, and two asked for the test without any psychological preparation. Conclusion: Along with the following of the protocol steps individual factors need to be taken into account in order to ideally plan the preparation process of presymptomatic testing. Authors recommend keeping contact with the individuals after genetic testing

The importance of the multiplex ligation-dependent probe amplification in the identification of a novel two-exon deletion of the NR5A1 gene in a patient with 46,XY differences of sex development

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