A new step in the French rare disease plan deployment: The ORPHA code has been introduced in French hospital information system databases
From 1 December 2012, hospitals - especially centres of reference for rare diseases – began one of the key actions of the Second French Plan for Rare Diseases, of using the ORPHA number for all hospitalised patients. The goal is to better identify patients in the healthcare system so as to improve knowledge of their healthcare pathways. Germany is also elaborating their National plan and foresee a similar initiative.
Since this decision was announced, the Orphanet team has received numerous requests from hospital staff and medical information departments responsible for the coding. Many would like to go beyond the initial instructions and immediately incorporate the entire Orphanet nomenclature into their system. There are several possibilities for accessing the ORPHA number and the nomenclature of rare diseases :
• Search by specific disease (the ORPHA number of the disease is displayed under its name on the encyclopaedia pages)
• Download all data in XML format from the "Diseases and cross-referencing" table on the Orphadata website (accessible from the Orphanet homepage under "Download our data")
• Download the new Orphanet Report Series with the list of rare diseases in alphabetical order. This document is available in French and in English, and will soon be available in German, Spanish, Italian and Portuguese.
Paradoxical association of autoinflammation and immunodeficiency in patients also presenting with muscular amylopectinosis
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The authors describe a new fatal, inherited pathology characterized by muscular amylopectinosis and the unique association of systemic autoinflammation and immunodeficiency. The muscular amylopectinosis manifest as intracellular glycogen inclusions complicated by myopathy and cardiomyopathy and the immunodeficiency as pyogenic bacterial infections. Identified in two unrelated families, this new disorder affects three patients, all carrying a HOIL1 mutation. The resulting LUBAC complex disruption induces IL-1 responses differing between cell types that may explain the immunodeficiency observed in some tissues and the autoinflammation caused in others.
Consult the PubMed abstract
Nature Immunology ; 13(12):1178-86 ; December 2012
First DPM2 deficiency identified in a muscular dystrophy–dystroglycanopathy syndrome with N-glycosylation or O-mannosylation defect
The authors report on three children from two families presenting with clinical signs of a muscular dystrophy–dystroglycanopathy syndrome and disorders of glycosylation, i.e. profound developmental delay, intractable epilepsy, severe hypotonia, progressive muscle weakness, joints contractures, progressive microcephaly, visual defects, facial dysmorphism, feeding difficulties, respiratory infections responsible for early fatal outcome (between 7 and 36 months of age). Hepatic involvement was found in one case. Biochemical analysis reveals deficient O-mannosylation in two patients and a defect in N-glycosylation in the other one. Having identified the first DPM2 deficiency in these three children, the authors propose to name this phenotype DPM2-CDG (Congenital Disorder of Glycosylation).
Consult the PubMed abstract
Annal of Neurology ; 72(4):550-8 ; October 2012
Severe encephalopathy with mild lactis acidosis associated with a PNPT1 mutation
A new mitochondrial disease has been characterized by the authors from the examination of two unrelated children born to consanguineous parents that did apparently well during the first months of life and then developed dystonia, dyskinesia, choreoathetosis, global hypotonia, severe muscle weakness, swallowing difficulties. They were diagnosed with a severe non progressive encephalopathy with mildly elevated plasma and cerebrospinal-fluid lactate. Measurement of respiratory chain function showed an important decrease of complexes III and IV activity in the liver of one of these children. A PNPT1 mutation impairing mitochondrial RNA import and translation was found in both. PMID :
Consult the PubMed abstract
American Journal of Human Genetics ; 2;91(5):912-8 ; November 2012
A skeletal overgrowth mediated by increase of cGMP level resulting from a NPR2 gain-of-function mutation
The authors have studied a family whose three members have tall stature, scoliosis, macrodactyly of the great toes, and minor clinodactyly in the fifth digit of the hands. All three patients exhibiting high blood cGMP concentrations and a NPR2 gain-of-function mutation, the authors consider that this mutation induces a skeletal overgrowth mediated by increase of cGMP level in chondrocytes.
Consult the PubMed abstract
PLoS One ; 7(8):e42180 ; 2012
Developmental delay, intellectual deficiency, and autistic behavior in seven patients with a HERC2 mutation
The authors describe seven patients belonging to three families who share a unique phenotype consisting of global developmental delay, intellectual deficiency, delayed adaptive hand use and independent ambulation, gait instability and autistic behavior. The authors observe that all these patients have blue irides. All of them also carry a mutation in the HERC2 gene located in a region of chromosome 15 associated with a group of neurodevelopmental diseases including Angelman syndrome whose manifestations resemble the phenotype described here.
Consult the PubMed abstract
Human Mutations ; 33(12):1639-46 ; December 2012
Autoinflammatory manifestations and immunodeficiency associated with a PLCG2 mutation
A new autoinflammatory disease has been characterized by the authors from the examination of a father and daughter. Both present with early onset recurrent blistering skin lesions. Manifesting in infancy as a full-body epidermolysis-bullosa-like eruption, these cutaneous disorders later evolved to recurrent erythematous plaques and vesiculopustular lesions worsening with heat and sun exposure. Other clinical features observed in these two individuals encompass non specific interstitial pneumonitis with respiratory bronchiolitis, arthralgia, ocular inflammation, enterocolitis, cellulitis and mild immunodeficiency resulting in sinopulmonary infections and low levels of circulating IgM and IgA. High-dose corticosteroids improve the inflammatory manifestations while nonsteroidal anti-inflammatory drugs and TNF inhibitors are inefficient. An IL-1 inhibitor induced a partial response. The two affected members of this family carry a gain-of-function mutation in PLCG2 that encodes an enzyme involved in regulation of immune responses.
Consult the PubMed abstract
American Journal of Human Genetics ; 91(4):713-20 ; October 2012
RMND1 mutations found in cases of encephalopathy associated with defects in oxidative phosphorylation and mitochondrial translation
An article published in October 2012 describes five infants born to consanguineous parents in the same family and suffering from severe neonatal encephaloneuromyopathy, lethargy, respiratory failure, profound floppiness, hyporeflexia or areflexia, equinus deformities, and lactic acidosis. They died in the two first years of life except for one case stillborn without skeletal anomalies. Genetic and biochemical analysis revealed an RMND1 (required for meiotic nuclear division 1) mutation, deficiencies of multiple mitochondrial respiratory-chain enzymes and defective mitochondrial translation. Another article also published on October 2012 report on a consanguineous family with two sisters affected by severe encephalopathy, lactic acidosis, and intractable seizures leading to early death, at 5 months of age for one of these two infants and at the age of 13 months for the other one. This study also identified an RMND1 mutation associated with defects in oxidative phosphorylation and mitochondrial translation. The mutations mentioned in these two publications don’t affect the same domain of RMND1.
Consult the PubMed abstracts
American Journal of Human Genetics ; 91(4):729-43, 91(4):729-36 ; October 2012
Aphonia in a multisystemic syndrome: a new entity may be associated with Cohen syndrome
A phenotype not matching any known pathology has been identified by the authors in a sister and brother whose parents are double first cousins. Both children present with congenital aphonia with vocal cord paralysis, optic atrophy, retinal dystrophy, deafness, inverted nipples, genital anomalies, growth retardation, intellectual disability, and distal limbs abnormalities including mildly broad thumbs and duplicated halluces. They also share particular facial features, i.e. thick eyebrows, ptosis, full eyelashes, long and downslanting palpebral fissures, short nose, full cheeks, small mouth, low-set, posteriorly rotated ears, and microstomia. As these clinical signs overlap with Cohen syndrome, the authors don’t exclude the hypothesis that both children are affected by two entities, one being Cohen syndrome and the other being unknown to date.
Consult the PubMed abstract
American Journal of Human Genetics ; 158A(11):2756-62 ; November 2012
A new hereditary form of gastric hypertrophy resembling Ménétrier disease
α
The authors have studied four generations of a family with cases presenting with clinical and endoscopic features of Ménétrier disease. However, given that the affected members exhibit neither protein loss nor increased levels of gastric TGF-, the authors estimate that they are facing a new hereditary form of gastric hyperplasia here transmitted in an autosomal dominant manner.
Consult the PubMed abstract
Journal of Pediatric Gastroenterologic Nutrition ; Jun 14 2012
A form of acromelanosis confirmed as distinct entity by a second case
The authors report on a 7-year-old boy affected by a cutaneous disorder manifesting a confetti-like hypopigmented macules firstly localized on the dorsal surface of the hands and feet, then spreading to the palms and soles a few months after birth. The young boy has a dark skin phototype (III-IV), a generalized hyperpigmentation more marked in the flexural areas and indifferent to sun exposure, and a reticulate hyperpigmentation in the auricles. Other clinical signs included strabismus convergens and keratosis pilaris. This phenotype is very similar to that described by Siemens in 1964 as acromelanosis albo-punctata. Thus the authors consider that it is a distinct entity and that this patient is only the second person affected by this pathology whose mode of inheritance remains uncertain.
Consult the PubMed abstract
Dermatology ; 224(4):331-9 ; 2012
Thalassemia International Federation World Congress
Date: 19-23 October 2013
Venue: Abu Dhabi, United Arab Emirates
Topics for this conference includes “all aspects of prevention, management and care of thalassemia and sickle cell disease and a one-day patient programme”.
For further details
Carpenter syndrome: MEGF8 mutations cause a subtype frequently associated with defective left-right patterning
American Journal of Human Genetics ; 91(5):897-905 ; November 2012
Autosomal recessive nonsyndromic sensorineural deafness type DFNB: PNPT1 mutations are more harmful than OTOG and OTOGL anomalies
American Journal of Human Genetics ; 91(5):919-27, 91(5):883-9, 91(5):872-82 ; November 2012
Pure hair and nail ectodermal dysplasia: HOXC13 mutations found in autosomal recessive forms
American Journal of Human Genetics ; 91(5):906-11 ; November 2012
MIDAS syndrome: COX7B, coding a cytochrome C oxidase subunit, found mutated in patients without microphthalmia
American Journal of Human Genetics ; 91(5):942-9 ; November 2012
Hereditary spastic paraplegia: five new genes responsible, some of them associated with new subtypes
American Journal of Human Genetics ; 91(6):1051-64, 91(6):1065-72, 91(6):1073-81 ; December 2012
J Med Genet ; 49(12):777-84 ; December 2012
Seckel syndrome: ATRIP mutations identified in one patient, and NIN (ninein) variants found associated with a microcephalic primordial dwarfism in two sisters
PLoS Genetics ; 8(11):e1002945 ; November 2012
J Clin Endocrinol Metab ; 97(11):E2140-51 ; November 2012
Juvenile primary lateral sclerosis: an ERLIN2 mutation suggesting a link with a pathology underlying motor neuron disorders
Annal of Neurology ; 72(4):510-6 ; October 2012
Dysosteosclerosis: SLC29A3 gene could impact osteoclast differenciation and function
Human Molecular Genetics ; 15;21(22):4904-9 ; November 2012
Autosomal dominant neovascular inflammatory vitreoretinopathy: CAPN5 mutations extend the range of calpains defects related diseases
PLoS Genetics ; 8(10):e1003001 ; October 2012
Severe intellectual disability: exome sequencing reveals involvement of GATAD2B and CTNNB1 genes and confirms that of DYNC1H1
N Engl J Med ; 367(20):1921-9 ; November 2012
Herpetic encephalitis: autosomal dominant TBK1 deficiency can cause a childhood form
Journal of Experimental Medicine ; 27;209(9):1567-82 ; August 2012
HELLP syndrome: a long intergenic noncoding RNA transcribed from 12q23.2 linked to familial cases, in which the fetal genotype determines the maternal phenotype
J Clin Invest ; 1;122(11):4003-11 ; November 2012
Craniosynostosis: ALX4 variants may have an impact on the genetic etiology of nonsyndromic forms
Hum Mutations ; 33(12):1626-9 ; December 2012
Anaplastic/large cell medulloblastoma: a ALK mutation found in a case of pediatric tumor with anaplasia
J Hum Genet ; 57(10):682-4 ; October 2012
Cataract, Coppock-like: a new GJA3 anomaly found in a family with a congenital form expand the mutation spectrum of this gene
Mol Vis ; 18:2114-8 ; 2012
De Hauwere syndrome: DNA sequencing and copy number analysis pinpointed a deletion involving FOXC1 in one patient
Eur J Hum Genet ; 20(12):1224-33 ; December 2012
Brachydactyly - elbow wrist dysplasia (Liebenberg syndrome): homeotic arm-to-leg transformation associated with genomic rearrangements at the PITX1 locus
American Journal of Human Genetics ; 5;91(4):629-35 ; October 2012
Autosomal recessive nonsyndromic sensorineural deafness type DFNB: a CABP2 splice-site mutation causes moderate-to-severe disease
American Journal of Human Genetics ; 5;91(4):636-45 ; October 2012
Autosomal recessive nonsyndromic sensorineural deafness type DFNB and Usher syndrome type 1: calcium signaling implicated through CIB2 mutations
Nat Genet ; 44(11):1265-71 ; November 2012
Primary ciliary dyskinesia: HYDIN, HEATR2, and LRRC6 identified as faulty genes, the former causing PCD without lateralisation defect
American Journal of Human Genetics ; 91(4):672-84, 91(4):685-93 ; October 2012
American Journal of Human Genetics ; 91(5):958-64 ; November 2012
Aicardi-Goutieres syndrome: identification of ADAR1 mutations, among which one also found in two cases with dyschromatosis symmetrica hereditaria
Nat Genet ; 44(11):1243-8 ; November 2012
Nonsyndromic pontocerebellar hypoplasia linked with CHMP1A mutations also inducing microcephaly
Nat Genet. ; 44(11):1260-1264. ; November 2012
Nocturnal frontal lobe epilepsy: KCNT1 mutations cause a severe form with early onset, intellectual disability and psychiatric features
Nat Genet ; 44(11):1188-90 ; November 2012
Malignant migrating partial seizures of infancy: KCNT1 mutations identified in 6 cases and a PLCB1 deletion found in another patient
Nat Genet ; 44(11):1255-9 ; November 2012
Epilepsia ; 53(8):e146-50 ; August 2012
Punctate palmoplantar keratoderma type 1: heterozygous AAGAB mutations cause very different forms may be in association with mutations in another gene
Am J Hum Genet ; 91(4):754-9 ; October 2012
Nat Genet ; 44(11):1272-6 ; November 2012
βShprintzen-Goldberg syndrome: mutations in exon 1 of SKI reveal a role of TGF- signaling
Nat Genet ; 44(11):1249-54 ; November 2012
Am J Hum Genet ; 91(5):950-7 ; November 2012
X-linked nonsyndromic intellectual deficit: HCFC1 implicated by a noncoding mutation affecting its expression
American Journal of Human Genetics ; 5;91(4):694-702 ; October 2012
Catecholaminergic polymorphic ventricular tachycardia: CALM1 mutations lead to early-onset form or CVPT-like arrhythmia
American Journal of Human Genetics ; 5;91(4):703-1 ; October 2012
Spinocerebellar ataxias type 19 and 22: due to mutations in the same gene, KCND3, both forms appear to be the same disease
Ann Neurol ; 72(6):870-80, 72(6):859-69 ; December 2012
Optic neuropathy: a novel missense SPG7 mutation identified in a large family with autosomal-dominant transmission
Brain. ; 135(Pt 10):2980-93 ; October 2012
Heterotaxia: BCL9L involved in a recessive visceral form associated with congenital heart disease
Sci Transl Med ; 4(154):154ra135 ; October 2012
MODY syndrome extends the spectrum of diabetes phenotypes associated with KCNJ11 mutations
PLoS One ; 7(6):e37423 ; 2012
Congenital isolated hyperinsulinism: HNF1A involved in two cases
J Clin Endocrinol Metab ; 97(10):E2026-30 ; October 2012
Osteogenesis imperfecta: identification of a locus in which a TMEM38B mutation is likely responsible for autosomal recessive forms
J Med Genet ; 49(10):630-5 ; October 2012
Joubert syndrome and related disorders: TMEM231 mutations found in cases with severe neurological defects, variable polydactyly and oculorenal features
J Med Genet ; 49(10):636-41 ; October 2012
Retinitis pigmentosa: a CYP4V2 mutation in a family with a form complicated with congenital cataract, corneal thinning and high myopia
PLoS One ; 7(5):e33673 ; 2012
Samaritan myopathy: a myopathy evolving to a benign form and whose causative mutation is located in the RYR1 gene
Acta Neuropathol. ; 124(4):575-81 ; October 2012
Autosomal dominant nonsyndromic intellectual deficit: truncating mutations in TCF4 can cause milder forms of intellectual disability
Clin Genet ; 83(2):198-200 ; February 2013
Central areolar choroidal dystrophy joins the group of choroidoretinal dystrophies that can be linked to a GUCY2D mutation
Invest Ophthalmol Vis Sci. ; 53(8):4748-53 ; July 2012
Muir-Torre syndrome: a MSH6 mutation identified in a form with multiple neoplasms and a lymphoma
J Clin Oncol. ; 30(22):e195-8 ; August 2012
Mayer-Rokitansky-Küster-Hauser syndrome: LHXI gene involved in a type II case after having been associated with a type I case
Hum Reprod. ; 27(9):2872-5 ; September 2012
Familial dyskinesia with facial myokymia likely results from a missense mutation in ADCY5
Arch Neurol ; 69(5):630-5 ; May 2012
Abruzzo-Erickson syndrome: role of TBX22 confirmed but the possibility that it is only responsible for palate defects remains to be excluded
Clin Genet. ; Epub ahead of print ; 11 July 2012
Multiminicore myopathy can result from MYH7 mutations, in particular when associated with cardiac involvement
Neuromuscul Disord. ; 22(12):1096-104 ; December 2012
Primary biliary cirrhosis: TNFSF15 and POU2AF1 identified as significant susceptibility loci in Japanese population
Am J Hum Genet ; 5;91(4):721-728 ; October 2012
Wegener granulomatosis and rheumatoid arthritis share CTLA4 as susceptibility locus
Arthritis Rheum. ; 64(10):3463-71. ; October 2012
Familial cerebral saccular aneurysm: NTM potential positional candidate gene for intracranial and thoracic aortic aneurysms
J Med Genet ; 49(10):621-9 ; October 2012
MOMO syndrome (Macrosomia, Obesity, Macrocephaly, and Ocular Abnormalities): LINC00237 first candidate gene suggested
Am J Med Genet ; 158A(11):2849-56 ; November 2012