Possible Causes for Severe Phenotype Progressive Myoclonic Epilepsy Type 3 OMIM : 56 Mutations in the KCTD7 gene cause a severe neurodegenerative phenotype characterized by onset of intractable myoclonic seizures before age 2 years and accompanied [malacards.org] Rohini Applied Biochemistry and Biotechnology (2013) Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease M. Traoré, G. [nature.com] Severer phenotype in Unverricht-Lundborg disease (EPM1) patients compound heterozygous for the dodecamer repeat expansion and the c.202C>T mutation in the CSTB gene. [thieme-connect.com] Autosomal Dominant Spastic Paraplegia Type 13 We first investigated a subgroup of ten subjects with a specific severe phenotype characterized by the following major features: hydrocephalus, mental retardation, spasticity [research.unipd.it] The disease may be caused by mutation in MFN2 and BSCL2 (associated with several phenotypes: CMT-2, Dhmn, Silver Syndrome [spastic-paraplegia with hand amyotrophy] and pure [sudanmedicalmonitor.org] […] genetic factors that cause and modify the severity of the phenotype. [wjgnet.com] Congenital Disorder of Glycosylation Type 1K […] manifestations or overall phenotypic severity) could be established. [mdpi.com] The COG5-8 gene exhibits a relative tolerance to loss of function variants (12), and its phenotypic severity is in line with the tolerance to other COG gene variants. [spandidos-publications.com] […] multi-system phenotypes. [preventiongenetics.com] Muscular Dystrophy-Dystroglycanopathy Type A7 WWS has a severe phenotype and death often occurs in the first year of life. [disorders.eyes.arizona.edu] It represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known [ncbi.nlm.nih.gov] Phenotypic spectrum of Fukutinopathy: most severe phenotype of Fukutinopathy. Brain Dev 2009;31(6):419-22. PMID 18834683 77 Yoshioka M, Saiwai S, Kuroki S, Nigami H. [medlink.com] Simpson-Golabi-Behmel Syndrome Type 2 This inheritance pattern is responsible for the more severe phenotype seen in the patient we describe above. [sciencerepository.org] For a general phenotypic description and a discussion of genetic heterogeneity of Simpson-Golabi-Behmel syndrome, see 312870. [ncbi.nlm.nih.gov] One such mechanism is skewed X inactivation in, which the wild-type gene is suppressed and a more severe phenotype results [2]. [sciencerepository.org] Autosomal Dominant Spastic Paraplegia Type 8 severity or age at onset. [academic.oup.com] to severe ones. [rarediseases.org] Interestingly, the patients in 7/8 families had a complex phenotype, with peripheral neuropathy, severe upper limb amyotrophy (Silver syndrome‐like), mental impairment, parkinsonism [doi.org] Developmental and Epileptic Encephalopathy Type 3 Mutations in the human X linked cyclin–dipendent kinase like 5 (CDKL5), infantile spasms and Rett (RTT) like phenotype. Initially normal EEG and severe hypotonia. [ijponline.biomedcentral.com] Deletions in the 9q33-q34 region have been reported in patients with early onset epileptic encephalopathy, but a consistent phenotype has yet to emerge. [ncbi.nlm.nih.gov] Several types of seizures or epileptic syndromes have been associated to IEMs with neonatal onset and associated to a variable phenotypic expression. [graphyonline.com] Bardet-Biedl Syndrome Type 10 Other studies have reported a more severe phenotype in those carrying the third mutation suggesting the possible effect of modifier allele. [patient.info] The patients with mutations in the latter genes seem to have a more severe renal phenotype compared with the patients with mutations in the BBSome. [cjasn.asnjournals.org] Thus, there is a general consensus that BBS patients with pathogenic variants in MKKS/BBS6, BBS10 and BBS12 genes develop a more severe phenotype than those with changes affecting [journal.frontiersin.org] Pontocerebellar Hypoplasia Type 10 […] progressive microcephaly, spasticity, seizures, and brain abnormalities, including brain atrophy, thin corpus callosum, and delayed myelination[12] PCH10 615803 CLP1 11q12.1 Severely [en.wikipedia.org] […] microcephaly, spasticity, seizures, and brain abnormalities, including brain atrophy and delayed myelination[13] Pontine and cerebellar hypoplasia is also observed in certain phenotypes [en.wikipedia.org] Early-Onset Alzheimer Disease Type 3 This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. [rarediseases.info.nih.gov] Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. [rarediseases.info.nih.gov] Infantile-Onset Pompe Disease An individualized, stepwise approach is recommended for IOPD management, and the dose of ERT depends on the severity of clinical phenotype and CRIM status. [ncbi.nlm.nih.gov] IoPD, the most severe form in the spectrum, is characterised by cardiomegaly, hypotonia, respiratory distress, and feeding difficulties, all of which can be attributed to [ncbi.nlm.nih.gov] In CRIM-positive Pompe patients with a mutation of mild effect and with less severe phenotype presentation, a lower dose of ERT (20 mg/kg/EOW) is suggested. [ncbi.nlm.nih.gov] 17q11 Microdeletion Syndrome Neurofibromatosis type I (NF1) microdeletion syndrome, which is present in 4–11% of NF1 patients, is associated with a severe phenotype as it is caused by the deletion of [moh-it.pure.elsevier.com] About 5%-10% of patients with neurofibromatosis diagnosis carry chromosomal microdeletions involving NF1, often presenting with a more severe phenotype than that observedin [pesquisa.bvsalud.org] Resumo: Introduction: Neurofibromatosis-Noonan syndrome is a clinical entity considered an extended Neurofibromatosis phenotype generally caused by different types of intragenic [bases.bireme.br] Cold-Induced Sweating Syndrome Type 1 The clinical phenotype was severe for all patients in this group (Table 1). [nature.com] The clinical phenotype was severe for all patients in this group ( Table 1 ). [nature.com] Although genotype/phenotype correlation has been elusive, it has been suggested that the level of the mutant protein may correlate with the phenotypic severity. [portal.findresearcher.sdu.dk] Mevalonate Kinase Deficiency Severe Phenotype of Mevalonate-kinase Deficiency in the Czech Republic [abstract]. [acrabstracts.org] The phenotype in our patients ranged from neonatal hydrops in the first patient to severe failure to thrive, hepatosplenomegaly, recurrent febrile episodes and lymphadenopathy [ncbi.nlm.nih.gov] phenotype and more common form, and mevalonic aciduria (MVA), a more severe phenotype and rare form. [ncbi.nlm.nih.gov] Glutamate Formiminotransferase Deficiency Features of a severe phenotype, first identified in patients of Japanese descent, include elevated levels of formiminoglutamate (FIGLU) in the urine in response to histidine [ncbi.nlm.nih.gov] There are two forms of the disorder: a severe phenotype and a mild phenotype. [egl-eurofins.com] Features of a severe phenotype, include elevated levels of formiminoglutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental [uniprot.org] Immunodeficiency Type 23 We thus report the most severe phenotype described so far associated with PGM3 mutations. [scilit.net] The patient's clinical phenotype is characterized by severe respiratory and cutaneous infections as well as developmental delay and severe mental retardation. [readbyqxmd.com] A Novel PGM3 Mutation Is Associated With a Severe Phenotype of Bone Marrow Failure, Severe Combined Immunodeficiency, Skeletal Dysplasia, and Congenital Malformations Guillermo [scilit.net] Mucopolysaccharidosis Type 2 The large deletion correlated with the severe phenotype of this Hunter syndrome patient. [ncbi.nlm.nih.gov] Complete lack of expression of IDS is consistent with the moderate to severe phenotype observed in this patient. [ncbi.nlm.nih.gov] Then, we examined the structural changes in IDS caused by P480R (phenotype: severe), P480L (phenotype: attenuated), D334G (phenotype: severe), and D334N (phenotype: attenuated [journals.plos.org] CINCA Syndrome It represents the most severe phenotype of the cryopyrin-associated periodic syndrome (CAPS).Clinical description and etiologyThe syndrome is due to autosomal dominant gain [semanticscholar.org] Within the spectrum of CAPS, the CINCA syndrome, also known as neonatal-onset multisystem inflammatory disease (NOMID), is considered to be the most severe phenotype. [jrheum.org] CINCA has the most severe phenotype with clinical features mimicking those of juvenile rheumatoid arthritis, including early onset, recurrent episodes of skin rash, fever, [medicaljournals.se] Monosomy 21q Abstract: Introduction 45,X karyotype is known to be related to more severe phenotype disorders, still comparative analysis of the karyotypes and phenotypes in Turner syndrome [lsmuni.lt] Deletions in the first region, ranging from the centromere to approximately 31.2 Mb (21q21.3), are associated with a severe phenotype. [molecularcytogenetics.biomedcentral.com] Three broad regions are implicated to the phenotype of monosomy 21. The first from the centromere to 31.2 Mb contains 50 genes and produces severe phenotype [ 13 ]. [omicsonline.org] Pelizaeus-Merzbacher Disease Most patients with missense mutations had a severe phenotype. [ncbi.nlm.nih.gov] It has therefore been hypothesized that absence of the protein should result in a less severe phenotype. [ncbi.nlm.nih.gov] The present patient showed severe phenotypic features that represent an intermediate form of PMD between classical and connatal forms. [ncbi.nlm.nih.gov] Piebaldism METHODS: As the proband and her mother showed a severe phenotype, we first chose to screen exons 10, 11, 12, 13, 16, 17 and 18 of the KIT proto-oncogene by direct sequencing [ncbi.nlm.nih.gov] This KIT mutation affects the intracellular tyrosine kinase domain and thus predicts a severe phenotype, as was the case in this family. [ncbi.nlm.nih.gov] Congenital Muscular Dystrophy Here we report that a de novo heterozygous deletion of the COL6A1 gene can also result in a severe phenotype of classical UCMD precluding ambulation. [ncbi.nlm.nih.gov] In this work, we report two novel homozygous mutations c.8005delT and c.8244+1G>A in the LAMA2 gene in four Tunisian patients with a severe MDC1A phenotype belonging to two [ncbi.nlm.nih.gov] Complete absence of this protein is usually associated with a severe phenotype characterized by drastic muscle weakness and characteristic changes in white matter in cerebral [ncbi.nlm.nih.gov] Cornelia De Lange Syndrome The genes involved in CdLS encode the cohesin complex and its associated proteins; and NIPBL mutations, which account for half of the cases, result in severe CdLS phenotypes [ncbi.nlm.nih.gov] Eight children had normal hearing, including one (12.5%) with a severe phenotype. [ncbi.nlm.nih.gov] Patients with NIPBL mutations had a more severe phenotype than those with mutations in SMC1A or those without identified mutations. [ncbi.nlm.nih.gov] Chromosome 19q13.11 Deletion Syndrome phenotype in patient 1 than in others concerning the presence of a disabling movement disorder and the severity of DD/ID. [nature.com] Constitutional del(19)(q12q13.1) in a three-year-old girl with severe phenotypic abnormalities affecting multiple organ systems. Am J Med Genet 1998;77:391–394. 14. [eymj.org] The cases with microdeletion of 19q13.11 share several common phenotypes and microdeletion of 19q13.11 is a recent emerging syndrome. [degruyter.com] Autosomal Recessive Centronuclear Myopathy The disease severity of our index case, carrying a c.1723A > T mutation, widens the phenotypic spectrum of AR CNM to include earlier loss of ambulation and respiratory failure [ncbi.nlm.nih.gov] Severe phenotype of a patient with autosomal recessive centronuclear myopathy due to a BIN1 mutation. [rarediseases.org] [11] Truncating mutations usually cause the severe neonatal form while non-truncating and missense mutations can lead to either mild or severe phenotype. [10], [11] Clinical [neurologyindia.com] Cryopyrin-Associated Periodic Syndrome Conversely, patients with a severe CINCA phenotype should be more aggressively treated since the beginning with a monthly administration of 4 mg/kg as the starting dose. [acrabstracts.org] The schedule of administration of canakinumab in cryopyrin associated periodic syndrome is driven by the phenotype severity rather than the age. [the-rheumatologist.org] Cryopyrin-associated periodic syndromes (CAPS) are linked to one single gene mutations, however they are associated with 3 syndromes, which are, from the mildest to the most severe [ncbi.nlm.nih.gov] Epidermolysis Bullosa Simplex The two patients with EBS carrying homozygous recessive mutations were affected by severe phenotypes and belonged to consanguineous families. [ncbi.nlm.nih.gov] These two biological pathways contribute both to the formation of the cell envelope barrier and seem to be defective in the severe EBS phenotype. [ncbi.nlm.nih.gov] The severe phenotype of the patients may be linked to the role of the N-terminal domain in the function of plectin and develops the understanding of the genotype-phenotype [ncbi.nlm.nih.gov] Muscular Dystrophy-Dystroglycanopathy Type B5 In general, mutants associated with severe clinical phenotypes are retained within the endoplasmic reticulum. [abcam.com] Muscular dystrophy-dystroglycanopathy congenital with or without mental retardation B5 (MDDGB5) [MIM:606612]: A congenital muscular dystrophy characterized by a severe phenotype [genecards.org] MDDGB5 is a congenital muscular dystrophy characterized by a severe phenotype with inability to walk, muscle hypertrophy, marked elevation of serum creatine kinase, a secondary [abcam.com] Congenital Muscular Dystrophy due to LMNA Mutation INTERPRETATION: The LMNA mutations identified appear to correlate with a relatively severe phenotype. [ncbi.nlm.nih.gov] Three of them had severe early-onset disease, no motor dcvelopinent, and the rest experienced development of a "dropped head" syndrome phenotype, Despite variable severity [discovery.ucl.ac.uk] Here, we identified a novel heterozygous LMNA p.R388P de novo mutation in a patient with a non-previously described severe phenotype comprising congenital muscular dystrophy [bioportfolio.com] Mucopolysaccharidosis Results showed a new mutation c.263A > C with the severe phenotype in homozygous in the patient. [ncbi.nlm.nih.gov] We aimed to design a method to determine phenotypic severity early in the disease course. [ncbi.nlm.nih.gov] Abstract A 2-year-old boy with an initial diagnosis of Hunter syndrome (mucopolysaccharidosis II) had a more severe phenotype than expected, which warranted further evaluation [ncbi.nlm.nih.gov]
