Abstract:
BACKGROUND:Inherited intellectual disability (ID) conditions are a group of genetically heterogeneous disorders that lead to variable degrees of cognition deficits. It has been shown that inherited ID can be caused by mutations in over 100 different genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying the defective gene underlying an autosomal recessive ID in two sibs of an Emirati family. METHODS:A combined approach involving homozygosity mapping and whole-exome sequencing was used to identify the causative mutation. RNA analysis was performed to gain further insight into the pathogenic effect of the detected mutation. RESULTS:We have identified a homozygous splicing mutation (c.1219_1222+1delAAAGG) in the LINS gene in the affected children. LINS is the human homologue of the Drosophila segment polarity gene lin that encodes an essential regulator of the wingless/Wnt signaling. The identified mutation alters the first consensus nucleotide of the 5' donor splice junction of intron 5 and the 3' end of exon 5. Transcript analysis revealed that this change leads to an exon skipping event resulting in direct splicing of exon 4 to exon 6. Another mutation in LINS has been described very briefly in an Iranian family with autosomal recessive ID and microcephaly. CONCLUSION:Our study confirms that LINS, a modulator of the WNT pathway, is an indispensable gene to human cognition and this finding sheds further light on the importance of WNT signaling in human brain development and/or function.
journal_name
Orphanet J Rare Disjournal_title
Orphanet journal of rare diseasesauthors
Akawi NA,Al-Jasmi F,Al-Shamsi AM,Ali BR,Al-Gazali Ldoi
10.1186/1750-1172-8-87subject
Has Abstractpub_date
2013-06-17 00:00:00pages
87issn
1750-1172pii
1750-1172-8-87journal_volume
8pub_type
杂志文章abstract:BACKGROUND:Achondroplasia is the most common form of disproportionate short stature and might affect not only the quality of life of the affected child but also that of the parents. OBJECTIVES:We aimed to investigate the quality of life of children with achondroplasia from child- and parent perspective as well as the ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1171-9
更新日期:2019-08-09 00:00:00
abstract:BACKGROUND:Orphan designated medicinal products benefit from regulatory and economic incentives for orphan drug development. Approximately 40% of orphan designations target rare neoplastic disorders, referring to rare cancers. In order to provide more insights in drugs for rare neoplastic disorders that are under devel...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-017-0578-4
更新日期:2017-02-16 00:00:00
abstract:BACKGROUND:Treatment of phenylketonuria (PKU) with sapropterin dihydrochloride in responsive patients from an early age can have many advantages for the patient over dietary restriction alone. Accordingly, approval of sapropterin in the European Union was extended in 2015 to include patients aged 0-4 years, bringing th...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-018-0911-6
更新日期:2018-09-29 00:00:00
abstract:BACKGROUND:Rare diseases are individually rare but globally affect around 6% of the population, and in over 70% of cases are genetically determined. Their rarity translates into a delayed diagnosis, with 25% of patients waiting 5 to 30 years for one. It is essential to raise awareness of patients and clinicians of exis...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-01493-7
更新日期:2020-08-12 00:00:00
abstract:BACKGROUND:Glycogenosis type II or Pompe disease is an autosomal-recessive lysosomal storage disease due to mutations in the gene encoding acid alpha-glucosidase (GAA), an enzyme required for lysosomal glycogen degradation. The disease predominantly affects the skeletal and respiratory muscles but there is growing evid...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-9-17
更新日期:2014-02-05 00:00:00
abstract:BACKGROUND:The activation of plasma enzyme systems contributes to hereditary angioedema attacks. We aimed to study the activation markers of the fibrinolytic, coagulation, and contact systems in a larger number of paired samples obtained from the same C1-INH-HAE patients in symptom-free periods and during attacks. MET...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-015-0351-5
更新日期:2015-10-09 00:00:00
abstract:BACKGROUND:The diagnosis of rare diseases poses a particular challenge to clinicians. This study analyzes whether patients' pain drawings (PDs) help in the differentiation of two pain-associated rare diseases, Ehlers-Danlos Syndrome (EDS) and Guillain-Barré Syndrome (GBS). METHOD:The study was designed as a prospectiv...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-01542-1
更新日期:2020-11-17 00:00:00
abstract:BACKGROUND:There are an established and growing number of Mendelian genetic causes for chronic kidney disease (CKD) in adults, though estimates of prevalence have been speculative. The CKD Queensland (CKD.QLD) registry enables partial clarification of this through the study of adults with CKD receiving nephrology care ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-9-98
更新日期:2014-06-30 00:00:00
abstract:BACKGROUND:The purpose of this study was to describe the natural history of severe congenital neutropenia (SCN) in 14 patients with G6PC3 mutations and enrolled in the French SCN registry. METHODS:Among 605 patients included in the French SCN registry, we identified 8 pedigrees that included 14 patients with autosomal...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-014-0183-8
更新日期:2014-12-10 00:00:00
abstract:BACKGROUND:Hereditary Haemorrhagic Telangiectasia (HHT) is a dominantly inheritable disorder, with a wide variety of clinical manifestations due to presence of multiple arteriovenous manifestations. The most common mutations are found in HHT1 (ENG) and HHT2 (ACVRL1) patients, causing alterations in the TGF-β pathway wh...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-016-0533-9
更新日期:2016-11-22 00:00:00
abstract:BACKGROUND:Alleviating the burden of rare diseases requires research into new diagnostic and therapeutic strategies. We undertook a systematic review to identify and compare the impact of stand-alone registries, registries with biobanks, and rare disease biobanks on research outcomes in rare diseases. METHODS:A system...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-018-0942-z
更新日期:2018-11-12 00:00:00
abstract:BACKGROUND:It has been suggested that ultra-rare diseases should be recognized as distinct from more prevalent rare diseases, but how drugs developed to treat ultra-rare diseases (DURDs) might be distinguished from drugs for 'other' rare diseases (DORDs) is not clear. We compared the characteristics of DURDs to DORDs f...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/s13023-018-0762-1
更新日期:2018-02-01 00:00:00
abstract:BACKGROUND:Many of the genetic childhood disorders leading to death in the pre- or neonatal period or during early childhood follow autosomal recessive modes of inheritance and bear specific challenges for genetic counseling and prenatal diagnostics. Parents are carriers but clinically unaffected, and diseases are rare...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-018-0763-0
更新日期:2018-01-26 00:00:00
abstract:BACKGROUND:Hepatic macrophage (Kupffer cell) hyperplasia is often described in Wilson's disease (WD). In many liver diseases, Kupffer cell activation is related to disease severity, liver function, and fibrosis but the importance in WD is unknown. Kupffer cell activation can be assessed by the P-concentration of solubl...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-018-0910-7
更新日期:2018-09-21 00:00:00
abstract:BACKGROUND:Acute hepatic porphyria (AHP) consists of three rare metabolic disorders. We investigated the risk of long-term sick leave, disability pension, and premature death in individuals with AHP compared to the general population. METHODS:In a nationwide cohort study from 1992 to 2017, records of 333 persons (tota...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1273-4
更新日期:2020-02-21 00:00:00
abstract:BACKGROUND:Major haemoglobinopathies (MH), such as thalassaemia syndromes (Thal) and sickle cell disorders (SCD), are genetic defects associated with chronic anaemia and other complications. In Europe, MH are rare diseases (RD) but their prevalence is significantly growing in many countries due to mobility and migratio...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-9-97
更新日期:2014-07-01 00:00:00
abstract:BACKGROUND:We sought to understand the experiences of parents/caregivers of children with inherited metabolic diseases (IMD) in order to inform strategies for supporting patients and their families. We investigated their experiences regarding the management of disease, its impact on child and family life, and interacti...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-016-0548-2
更新日期:2016-12-07 00:00:00
abstract:BACKGROUND:Rubinstein-Taybi syndrome (RTS) is a rare, congenital, plurimalformative, and neurodevelopmental disorder. Previous studies have reported that large deletions contribute to more severe RTS phenotypes than those caused by CREBBP point mutations, suggesting a concurrent pathogenetic role of flanking genes, typ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-01378-9
更新日期:2020-04-22 00:00:00
abstract:BACKGROUND:Approximately 20% of adrenoleukodystrophy (X-ALD) female carriers may develop clinical manifestations, typically consisting of progressive spastic gait, sensory deficits and bladder dysfunctions. A skewing in X Chromosome Inactivation (XCI), leading to the preferential expression of the X chromosome carrying...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-7-10
更新日期:2012-01-26 00:00:00
abstract:BACKGROUND:Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare disease, characterized by the massive accumulation of triglyceride (TG) in multiple tissues, especially skeletal muscle, heart muscle and the coronary artery. TGCV is caused by mutation of adipose triglyceride lipase, which is an essential molecule ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-8-197
更新日期:2013-12-21 00:00:00
abstract:BACKGROUND:Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscle disorder, which is linked to the contraction of the D4Z4 array at chromosome 4q35. Recent studies suggest that this shortening of the D4Z4 array leads to aberrant expression of double homeobox protein 4 (DUX4) and causes FSHD. In a...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-8-55
更新日期:2013-04-05 00:00:00
abstract::Taliglucerase alfa is an enzyme replacement therapy (ERT) approved for treatment of adult and paediatric patients with Type 1 Gaucher disease (GD) in several countries and the first plant cell-expressed recombinant therapeutic protein approved by the US Food and Drug Administration for humans. Here, we review the find...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/s13023-018-0776-8
更新日期:2018-02-23 00:00:00
abstract::IgA pemphigus is an exceedingly rare autoimmune blistering disorder, caused by IgA autoantibodies against desmosomal proteins. No treatment option has been found to be universally effective. The disease is often recalcitrant to oral steroids and immunosuppressants. Here, we describe the use of systemic retinoids for t...
journal_title:Orphanet journal of rare diseases
pub_type: 信件
doi:10.1186/s13023-018-0899-y
更新日期:2018-09-18 00:00:00
abstract::Chronic intestinal pseudo-obstruction (CIPO) is a rare intestinal motility disorder with significant morbidity and mortality in pediatric patients. The diagnosis of CIPO is difficult, because it is clinically based on the symptoms and signs of bowel obstruction which are similar to the clinical manifestations of other...
journal_title:Orphanet journal of rare diseases
pub_type: 信件
doi:10.1186/s13023-017-0615-3
更新日期:2017-03-28 00:00:00
abstract:BACKGROUND:Prader-Willi syndrome (PWS) is a complex neurodevelopmental genetic disorder with hypothalamic dysfunction, early morbid obesity with hyperphagia, and specific psychiatric phenotypes including cognitive and behavioural problems, particularly disruptive behaviours and frequent temper outbursts that preclude s...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,随机对照试验
doi:10.1186/1750-1172-6-47
更新日期:2011-06-24 00:00:00
abstract:BACKGROUND:The lysosomal storage disorder, Niemann Pick type C1 (NPC1), presents a variable phenotype including neurovisceral and neurological symptoms. 2-Hydroxypropyl-ß-cyclodextrin (HPßCD)-based therapies are presently the most promising route of intervention. While severe cerebellar dysfunction remains the main dis...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-015-0348-0
更新日期:2015-10-12 00:00:00
abstract:BACKGROUND:In Taiwan, DNA-based newborn screening showed a surprisingly high incidence of a cardiac Fabry mutation (IVS4 + 919G > A). The prevalence of this mutation is too high to be believed that it is a real pathogenic mutation. The purpose of this study is to identify the cardiac pathologic characteristics in patie...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-9-96
更新日期:2014-07-01 00:00:00
abstract:PURPOSE:Several gene therapy trials for Duchenne muscular dystrophy initiated in 2018. Trial decision making is complicated by non-curative, time-limited benefits; the progressive, fatal course; and high unmet needs. Here, caregivers and patients prioritize factors influencing decision making regarding participation in...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1069-6
更新日期:2019-05-09 00:00:00
abstract:OBJECTIVE:NUT midline carcinoma (NMC), a rare type of squamous cell carcinoma, is genetically characterised by NUT midline carcinoma family member 1 (NUTM1) gene rearrangement. NMC can arise from the lungs; however, there is no standard for the management of primary pulmonary NMC. This study aimed to confirm the clinic...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-01449-x
更新日期:2020-07-10 00:00:00
abstract:BACKGROUND:Stiff Person Syndrome (SPS) is a rare autoimmune movement disorder characterized by the presence of autoantibodies specific to the smaller isoform of glutamate decarboxylase (GAD65). A pathological role of these antibodies has been suggested by their capacity to inhibit GAD65 enzyme activity and by the obser...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-8-82
更新日期:2013-06-05 00:00:00