Abstract:
:Primary cilia are microtubule-rich hair-like extensions protruding from the surface of most post-mitotic cells. They act as sensory organelles that help interpret various environmental cues. Mutations in genes encoding proteins involved in ciliogenesis or protein transport to the primary cilia lead to a wide variety of diseases commonly referred to as ciliopathies,which include primary ciliary dyskinesia, situs invertus, hydrocephalus, kidney diseases, respiratory diseases, and retinal degenerations. In the retina, the photoreceptor cells have a highly specialized primary cilium called the outer segment (OS), which is essential for photosensation. Development of the photoreceptor OS shares key regulatory mechanisms with ciliogenesis in other cell types. Accumulating evidence indicates that mutations that affect OS development and/or protein transport to the OS generally lead to photoreceptor degeneration, which can be accompanied by a range of other clinical manifestations due to the dysfunction of primary cilia in different cell types. Here, we review the general mechanisms regulating ciliogenesis, and present different examples of mutations affecting OS ciliogenesis and protein transport that lead to photoreceptor degeneration. Overall, we conclude that the genetic and molecular evidence accumulated in recent years suggest a clear link between the development and function of the primary cilium and various clinical conditions. Future studies aimed at uncovering the cellular and molecular mechanisms implicated in ciliogenesis in a wide variety of animal models should greatly increase our understanding of the pathophysiology of many human diseases, including retinal degenerations.
journal_name
Clin Genetjournal_title
Clinical geneticsauthors
Ramamurthy V,Cayouette Mdoi
10.1111/j.1399-0004.2009.01240.xsubject
Has Abstractpub_date
2009-08-01 00:00:00pages
137-45issue
2eissn
0009-9163issn
1399-0004journal_volume
76pub_type
杂志文章,评审abstract::A total of 509 specimens of spontaneous abortion were studied. Of 364 complete specimens, 15 (4.1%) had central nervous system (CNS) abnormalities. The defects which were seen were anencephaly, spina bifida, iniencephaly, encephalocele and anencephaly combined with complete rachischisis. A high proportion (five out of...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1978.tb04136.x
更新日期:1978-05-01 00:00:00
abstract::A seven-generation pedigree of apparent X-linked, nonspecific mental retardation is reported. There are 19 known affected males who appear to have received the gene through normal mothers. Retardation, lack of fine motor coordination, hyperactivity and a speech defect are the characteristics of affected individuals st...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1976.tb01557.x
更新日期:1976-02-01 00:00:00
abstract::In all known congenital imprinting disorders an association with aberrant methylation or mutations at specific loci was well established. However, several patients with transient neonatal diabetes mellitus (TNDM), Silver-Russell syndrome (SRS) and Beckwith-Wiedemann syndrome (BWS) exhibiting multilocus hypomethylation...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2010.01514.x
更新日期:2011-07-01 00:00:00
abstract::The 15q13.3 microdeletion syndrome (OMIM #612001) is characterized by a wide range of phenotypic features, including intellectual disability, seizures, autism, and psychiatric conditions. This deletion is inherited in approximately 75% of cases and has been found in mildly affected and normal parents, consistent with ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2012.01925.x
更新日期:2013-04-01 00:00:00
abstract::Apolipoprotein E from human serum shows a genetic polymorphism determined by two autosomal codominant alleles, Apo En and Apo Ed. Homozygosity for the gene Apo Ed (phenotype Apo E-D) results in primary dysbetalipoproteinemia, but only some individuals with this phenotype develop gross hyperlipidemia (hyperlipoproteine...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract::The 13 subtypes of oral-facial-digital syndrome (OFDS) belong to the heterogeneous group of ciliopathies. Disease-causing genes encode for centrosomal proteins, components of the transition zone or proteins implicated in ciliary signaling. A unique consanguineous family presenting with an unclassified OFDS with skelet...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12785
更新日期:2016-12-01 00:00:00
abstract::In an ethnically-homogeneous population, it is valuable to identify founder mutations in cancer-predisposing genes. Founder mutations have been found in four breast-cancer-predisposing genes in French-Canadian breast cancer families. The frequencies of the mutant alleles have been measured neither in a large series of...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2009.01277.x
更新日期:2009-11-01 00:00:00
abstract::A two-year-old female with the Pierre Robin anomaly and bilateral index finger malformations is described. Hypertelorism, full cheeks, posteriorly rotated ears with prominent antihelix, short neck, simian creases, bilateral fifth finger clinodactyly, and short toes with hypoplastic small nails were also present. Her m...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1986.tb01244.x
更新日期:1986-02-01 00:00:00
abstract::The activity of phytanic acid oxidase is low in infantile and adult Refsum's disease, and in the cerebro-hepato-renal (Zellweger's) syndrome. The plasma of patients with the infantile but not the adult form of Refsum's disease contains increased amounts of pipecolic acid and of at least two abnormal bile acids, one of...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1984.tb01107.x
更新日期:1984-12-01 00:00:00
abstract::Hunter syndrome or mucopolysaccharidosis type II (MPSII) is caused by pathogenic variants in the IDS gene. This is the first study that examines the mutational spectrum in 25 unrelated Mexican MPSII families. The responsible genotype was identified in 96% of the families (24/25) with 10 novel pathogenic variants: c.13...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12738
更新日期:2016-05-01 00:00:00
abstract::Steatocystoma Multiplex (S.M.) is an inherited condition characterized by the appearance of cysts during the first or second decade of life. Familial cases have occasionally been reported. We studied 13 patients affected by S.M. from two unrelated families, focusing our attention on HLA, Gm and Km genotypes and on chr...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1989.tb03176.x
更新日期:1989-08-01 00:00:00
abstract::Metacarpophalangeal pattern profile (MCPP) analysis was applied to patients with Pfeiffer and Chotzen syndromes, dominantly inherited types of acrocephalosyndactyly (ACS). A characteristic MCPP was obtained for the group. However, it did not discriminate between patients with Chotzen syndrome and those with Pfeiffer s...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1977.tb01316.x
更新日期:1977-04-01 00:00:00
abstract::Cutis laxa is described in three cases: a 17-year-old man, his mother and his maternal grandmother. The onset of skin symptoms occurred from puberty to early adulthood. The skin was loose-hanging, wrinkled and without elasticity. X-ray examination showed numerous gastrointestinal diverticulae in the two older patients...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1991.tb03038.x
更新日期:1991-05-01 00:00:00
abstract::Cross syndrome is a rare syndrome characterized by ocular and cutaneous hypopigmentation and neurological manifestations. A few reports have been published since 1967. In this report, we present a new case of Cross syndrome with additional findings such as urinary tract abnormality, bilateral inguinal hernia, focal in...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1111/j.1399-0004.1997.tb02432.x
更新日期:1997-02-01 00:00:00
abstract::The locus DXS255 was studied using the probe M27 beta in ten probands with Rett syndrome and in eight of their families. No evidence of uniparental disomy of the X chromosome was detected, as all informative probands had inherited an allele from each of their parents. Differential methylation of a CCGG site within the...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1993.tb03889.x
更新日期:1993-11-01 00:00:00
abstract::Two brothers showed ichthyosis, bilateral cryptorchidism, hypogenitalism and mental retardation. In addition, the younger brother had short stature associated with disorders of secretions of insulin, ACTH and GH. This is the third reported case of the syndrome of ichthyosis and hypogonadism. ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1976.tb01583.x
更新日期:1976-03-01 00:00:00
abstract::The aim of this study was to search for SLC40A1 mutations in iron overloaded patients, which tested negative for HFE mutations and other iron-related genes. After a careful differential diagnosis, we selected 56 patients with unexplained iron overload whose phenotype could suggest the ferroportin disease. Iron overloa...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2007.00950.x
更新日期:2008-02-01 00:00:00
abstract::We describe 2 patients with Angelman syndrome (AS) due to paternal uniparental disomy (UPD). One patient is a female aged 30 years and the other a male aged 4 1/2 years. Both have the characteristic wide mouth and big chin, moderate mental retardation, virtually no speech but some 30 words of sign language and a happy...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1998.tb02682.x
更新日期:1998-03-01 00:00:00
abstract::We recently described a complex multisystem syndrome in which mild-moderate myopia segregated as an independent trait. A plethora of genes has been related to sporadic and familial myopia. More recently, in Chinese patients severe myopia (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene. Seven family mem...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.13217
更新日期:2018-05-01 00:00:00
abstract::Mental retardation affects 1-3% of the general population, and the genetic causes in many cases are unknown. Cytogenetically undetected chromosomal imbalances have been indicated as an explanation. Nowadays, due to the development of molecular cytogenetic techniques, it is possible to identify cryptic rearrangements i...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j..2004.00167.x
更新日期:2004-01-01 00:00:00
abstract::Few studies have investigated the frequency of hereditary non-polyposis colorectal cancer (HNPCC) in patients with colorectal cancer (CRC), and these have shown marked geographic variations. The aim of this study was to estimate the frequency of HNPCC in a cohort of Uruguayan CRC patients. We included all patients ope...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2005.00458.x
更新日期:2005-07-01 00:00:00
abstract::To determine the mutations of Southern Chinese with Duchenne and Becker muscular dystrophies (DMD, BMD), we analysed 28 DMD and BMD patients in 24 unrelated families for intragenic deletions and duplications by using cDNA probes covering the entire 14 kb of the dystrophin gene. Deletions were detected in nine unrelate...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1992.tb03676.x
更新日期:1992-05-01 00:00:00
abstract::The incidence of pancreatic ductal adenocarcinoma (PDAC) is steadily increasing and the annual death-to-incidence ratio approaches one. This is a figure that has not changed for several decades. Surgery remains the only chance of cure; however, only less than 20% of patients are amenable to operative resection. Despit...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1111/cge.12536
更新日期:2015-09-01 00:00:00
abstract::Phytohaemagglutinin induces interferon-gamma synthesis in lymphocyte cultures from healthy individuals. We report two sibs with recurrent infections, selective IgA deficiency, and reduced blast transformation index under PHA-stimulation, without interferon-gamma response. ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1988.tb03480.x
更新日期:1988-06-01 00:00:00
abstract::Fabry disease (FD) is an X-linked lysosomal storage disorder (LSD) caused by the deficiency of the enzyme α-galactosidase. It exhibits a wide clinical spectrum that may lead to a delayed or even missed diagnosis and the real incidence can be underestimated. We report the cases of two unrelated Italian families in whom...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12071
更新日期:2013-09-01 00:00:00
abstract::An autosomal dominant (AD) antecubital pterygium syndrome has been documented on the Indian Ocean Island of Rodrigues, and 11 affected family members in five generations have been studied over four decades. The consistent features include a fleshy web extending across the anterior aspect of the cubital fossa, absence ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1988.tb02617.x
更新日期:1988-07-01 00:00:00
abstract::Female heterozygotes for the fragile X syndrome show variable levels of mental handicap from normal to severely retarded. The degree to which they are affected may depend upon whether the fragile or the normal X chromosome is preferentially inactivated, but one of the problems with the use of BUdR for the study of Lyo...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1989.tb03362.x
更新日期:1989-07-01 00:00:00
abstract::A sample of psychotic and prepsychotic twins is presented, based on 9000 patients born during 1930--1946 and admitted to psychiatric departments in Scania, Sweden, during the 1960's. All twins of the same sex (76 pairs) were registered and their records examined. Twenty-three complete pairs, where one or both twins sh...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1981.tb00728.x
更新日期:1981-05-01 00:00:00
abstract::During three years, 39,924 infants born consecutively in the area covered by our registry of congenital malformations were surveyed; 775 had major congenital malformations. Recurrence risks for the major malformation was estimated and classified as high (greater than 10%, 5.3% of the cases), low (1 to 10%, 85.3% of th...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1986.tb00813.x
更新日期:1986-03-01 00:00:00
abstract::Several sequence variations were examined for being endogenous "risk markers" in the development of CHD. The "markers" in this study included: the PstI-SstI RFLPs in the apo AI-CIII gene cluster, the EcoRI-MspI RFLPs in the apo B100 gene and the SstI RFLP in the 5' flanking region of the insulin gene. The study popula...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1995.tb03957.x
更新日期:1995-04-01 00:00:00