Complete recovery from psychosis upon miglustat treatment in a juvenile Niemann-Pick C patient

L

Successful surgical intervention in a case of spontaneous chylothorax in an infant unresponsive to conservative therapy

L

Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth

L

PRIM1 Deficiency Causes a Distinctive Primordial Dwarfism Syndrome

DNA replication is fundamental for cell proliferation in all organisms. Nonetheless, components of the replisome have been implicated in human disease, and here we report PRIM1 encoding the catalytic subunit of DNA primase as a novel disease gene. Using a variant classification agnostic approach, biallelic mutations in PRIM1 were identified in five individuals. PRIM1 protein levels were markedly reduced in patient cells, accompanied by replication fork asymmetry, increased interorigin distances, replication stress, and prolonged S-phase duration. Consequently, cell proliferation was markedly impaired, explaining the patients' extreme growth failure. Notably, phenotypic features distinct from those previously reported with DNA polymerase genes were evident, highlighting differing developmental requirements for this core replisome component that warrant future investigation

Pompe-kór fenotípusvariációi, kórlefolyása és az enzimpótló kezelés eredményei: hazai tapasztalatok

A Pompe-kór kialakulásáért az alfa-glikozidáz enzim autoszomális recesszíven öröklődő hiánya, illetve kóros működése felelős. Célok és módszerek: A szerzők tanulmányukban 11, Pompe-kórral diagnosztizált magyar beteg klinikai fenotípusát elemezték, és nyolc esetben az enzimpótló kezelés melletti hosszmetszeti megfigyelés eredményeit értékelték. Eredmények: Egy betegben az első tünet már az újszülöttkorban jelentkezett, kezdeti cardiomyopathia és nagyon enyhe izomhypotonia formájában. A korai kezdet ellenére a progresszió nagyon lassú volt: négyéves korától részesült enzimpótló kezelésben, hatévesen motoros deficit már nem volt észlelhető. Egy beteg 2,5 évesen tünetmentes. A felnőttkori formákban 20 és 50 év között kezdődtek az első tünetek, a végtagövi izomgyengeség spektruma az enyhétől a súlyos érintettségig terjedt. Három esetben légzési elégtelenséget észleltek. Az enzimpótló terápiát a legtöbb esetben szignifikáns izomerő-fokozódás és a légzési működés javulása követte. Következtetések: Hazai Pompe-kóros betegekre a fenotípus széles variabilitása jellemző. Korai enzimpótló kezeléssel egy gyermek esetében teljes tünetmentességet, előrehaladott állapotú légzési elégtelenségben szenvedő betegnél az önálló légzés visszanyerését, és ezáltal jelentős életminőség-nyereséget lehetett elérni. Orv. Hetil., 2011, 152, 1569–1575. | Pompe’s disease is an autosomal recessive disease caused by deficiency of acid-alpha-glucosidase. Aims and Methods: Authors analyzed the phenotype of 11 Hungarian patients with Pompe’s disease and evaluated clinical parameters and response to enzyme replacement therapy during a long-term follow-up in 8 patients. Results: One patient with atypical infantile form presented with cardiomyopathy and a very slow progression of motor deficits; after 2 years of enzyme replacement therapy no disability was present at the age 6 years. Another patient was asymptomatic at the age of 2.5 years. The adult onset form was characterized by slight to prominent limb-girdle myopathy with an age of onset between 20 and 50 years. In 3 of such cases respiratory insufficiency was also present. Conclusions: Hungarian patients with Pompe’s disease presented with a wide phenotypic variability ranging from atypical early childhood form with slowly progressive course to late-onset limb-girdle myopathy with variable courses. Enzyme replacement therapy resulted in significant improvement in motor and respiratory functions in most of the patients. Orv. Hetil., 2011, 152, 1569–1575

Diagnosis and management in Rubinstein-Taybi syndrome:first international consensus statement

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care.</p

Diagnosis and management in Rubinstein-Taybi syndrome:first international consensus statement

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care.</p

Diagnosis and management in Rubinstein-Taybi syndrome: first international consensus statement

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care