Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Exome sequencing identifies a mutation in OFD1 in a male with Joubert syndrome, orofaciodigital spectrum anomalies and complex polydactyly.

ABSTRACT: Orofaciodigital syndrome type 1 or oral-facial-digital syndrome type 1 (OFDS1, OMIM #311200) is an X-linked malformation syndrome caused by hemizygous mutations in the OFD1 (OMIM #300170) gene with presumed male lethality. Recently males with OFDS1 and mutations in OFD1 have been described. We report a 17-year-old male with molar tooth sign, small cerebellum with absence of the cerebellar vermis, complex polydactyly with a Y-shaped metacarpal, renal failure and craniofacial anomalies caused by a novel splice-mutation (c.1129+4A>T) in the OFD1 gene identified by exome sequencing.

SUBMITTER: Wentzensen IM

PROVIDER: S-EPMC4760119 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Exome sequencing identifies a mutation in OFD1 in a male with Joubert syndrome, orofaciodigital spectrum anomalies and complex polydactyly.

Wentzensen Ingrid M IM Johnston Jennifer J JJ Patton John H JH Graham John M JM Sapp Julie C JC Biesecker Leslie G LG

Human genome variation 20160204

Orofaciodigital syndrome type 1 or oral-facial-digital syndrome type 1 (OFDS1, OMIM #311200) is an X-linked malformation syndrome caused by hemizygous mutations in the OFD1 (OMIM #300170) gene with presumed male lethality. Recently males with OFDS1 and mutations in OFD1 have been described. We report a 17-year-old male with molar tooth sign, small cerebellum with absence of the cerebellar vermis, complex polydactyly with a Y-shaped metacarpal, renal failure and craniofacial anomalies caused by a ...[more]

PMID: 27081566

Similar Datasets

Exome sequencing identifies novel mutations in C5orf42 in patients with Joubert syndrome with oral-facial-digital anomalies.

Project description:Oral-facial-digital syndrome VI (OFD6 OMIM #277170), also called Varadi-Papp syndrome, is a ciliopathy inherited in an autosomal recessive pattern. Recently, mutations in C5orf42 (OMIM #614571) have been associated with OFD6. OFD6 overlaps with Joubert syndrome and mutations in C5orf42 were described in Joubert syndrome 17 (JBTS17, OMIM #614571). Using exome sequencing we report three novel variants and one previously reported variant in the C5orf42 gene in patients with OFD6.

| S-EPMC4785546 | biostudies-literature

Expanding the molecular basis and phenotypic spectrum of X-linked Joubert syndrome associated with OFD1 mutations.

Project description:Using a combination of linkage mapping and massively parallel sequencing of the X-chromosome exome, we identified an 18-bp deletion in exon 8 of the oral-facial-digital syndrome type 1 (OFD1) gene in a family with X-linked Joubert syndrome (JBTS10). The deletion results in an in-frame deletion of six amino acids. New features not noted in the two previously reported cases of X-linked Joubert syndrome include the presence of polycystic kidney disease, polymicrogyria and hydrocephalus. Our study further underlines the power of genetic mapping combined with massively parallel sequencing as a powerful tool for novel disease gene and mutation discovery.

| S-EPMC3376274 | biostudies-literature

An Orofaciodigital Syndrome 1 Patient and Her Mother Carry the Same OFD1 Mutation but Have Different X Chromosome Inactivation Patterns.

Project description:Orofaciodigital syndrome 1 (OFD-1) is a rare, X-linked, dominantly inherited disorder caused by an OFD1 mutation that can cause polycystic kidneys. A 37-year-old woman on hemodialysis therapy was admitted to our hospital for trans-catheter arterial embolization therapy for enlarged polycystic kidneys. Lobulated tongue and brachydactyly were noticed, prompting an OFD1 sequencing analysis. Sequencing revealed a causal four-base-pair deletion in exon 13, both in the patient and in her mother, whose renal function had been retained. The peripheral leukocyte X chromosome inactivation pattern was skewed in the patient but not in her mother, suggesting some role in their phenotypic difference.

| S-EPMC6859397 | biostudies-literature

Mutation spectrum of Joubert syndrome and related disorders among Arabs.

Project description:Joubert syndrome (JS) is a rare autosomal recessive (AR), neurological condition characterized by dysgenesis of the cerebellar vermis with the radiological hallmark of molar tooth sign, oculomotor apraxia, recurrent hyperventilation and intellectual disability. Most cases display a broad spectrum of additional features, including polydactyly, retinal dystrophy and renal abnormalities, which define different subtypes of JS-related disorders (JSRDs). To date, 23 genes have been shown to cause JSRDs, and although most of the identified genes encode proteins involved in cilia function or assembly, the molecular mechanisms associated with ciliary signaling remain enigmatic. Arab populations are ethnically diverse with high levels of consanguinity (20-60%) and a high prevalence of AR disorders. In addition, isolated communities with very-high levels of inbreeding and founder mutations are common. In this article, we review the 70 families reported thus far with JS and JSRDs that have been studied at the molecular level from all the Arabic countries and compile the mutations found. We show that JS and the related JSRDs are genetically heterogeneous in Arabs, with 53 mutations in 15 genes. Thirteen of these mutations are potentially founder mutations for the region.

| S-EPMC4785524 | biostudies-literature

Exome sequencing identifies a spectrum of mutation frequencies in advanced and lethal prostate cancers.

Project description:To catalog protein-altering mutations that may drive the development of prostate cancers and their progression to metastatic disease systematically, we performed whole-exome sequencing of 23 prostate cancers derived from 16 different lethal metastatic tumors and three high-grade primary carcinomas. All tumors were propagated in mice as xenografts, designated the LuCaP series, to model phenotypic variation, such as responses to cancer-directed therapeutics. Although corresponding normal tissue was not available for most tumors, we were able to take advantage of increasingly deep catalogs of human genetic variation to remove most germline variants. On average, each tumor genome contained ~200 novel nonsynonymous variants, of which the vast majority was specific to individual carcinomas. A subset of genes was recurrently altered across tumors derived from different individuals, including TP53, DLK2, GPC6, and SDF4. Unexpectedly, three prostate cancer genomes exhibited substantially higher mutation frequencies, with 2,000-4,000 novel coding variants per exome. A comparison of castration-resistant and castration-sensitive pairs of tumor lines derived from the same prostate cancer highlights mutations in the Wnt pathway as potentially contributing to the development of castration resistance. Collectively, our results indicate that point mutations arising in coding regions of advanced prostate cancers are common but, with notable exceptions, very few genes are mutated in a substantial fraction of tumors. We also report a previously undescribed subtype of prostate cancers exhibiting "hypermutated" genomes, with potential implications for resistance to cancer therapeutics. Our results also suggest that increasingly deep catalogs of human germline variation may challenge the necessity of sequencing matched tumor-normal pairs.

| S-EPMC3193229 | biostudies-literature

Erratum: Mutation spectrum of Joubert syndrome and related disorders among Arabs.

Project description:[This corrects the article DOI: 10.1038/hgv.2014.20.].

| S-EPMC4785561 | biostudies-other

Diagnosis of Joubert Syndrome 10 in a Fetus with Suspected Dandy-Walker Variant by WES: A Novel Splicing Mutation in OFD1.

Project description:Joubert syndrome (JBTS) is a clinically and genetically heterogeneous group of ciliary diseases. To date, 34 subtypes of JBTS have been classified due to different causative genes or extra clinical features. Most of them are autosomal recessive, while only the subtype 10 (JBTS10) is a quite rare X-linked recessive disorder caused by OFD1 mutations with few reports. In this study, by using whole exome sequencing (WES), a novel OFD1 splicing mutation (c.2488+2T>C) was identified in a male fetus with suspected Dandy-Walker variant (DWV) and syndactyly, for whom abnormal karyotype and pathogenic CNV have been excluded. This mutation was inherited from the mother who has experienced two similar pregnancies before. An abnormal skipping of exon 18 in OFD1 mRNA was confirmed by RT-PCR and sequencing. Result from quantitative RT-PCR also showed that total OFD1 mRNA in the index fetus was significantly lower than the control. After a combined analysis of genetic testing results and genotype-phenotype correlations, the novel mutation c.2488+2T>C in OFD1 was considered to be the genetic cause for the affected fetus. Thus the diagnosis should be JBTS10 rather than the primary clinical diagnosis of DWV. We report the first prenatal case of JBTS10 in Chinese population, which not only helps the family to predict recurrence risks for future pregnancies but also provides more information for understanding such a rare disease. The results also present evidence that WES is an effective method in prenatal diagnosis for those fetuses with Joubert syndrome.

| S-EPMC6276521 | biostudies-literature

Whole exome sequencing identifies multiple diagnoses in congenital glaucoma with systemic anomalies.

Project description:The genetic basis of congenital glaucoma with systemic anomalies is largely unknown. Whole exome sequencing (WES) in 10 probands with congenital glaucoma and variable systemic anomalies identified pathogenic or likely pathogenic variants in three probands; in two of these, a combination of two Mendelian disorders was found to completely explain the patients' features whereas in the third case only the ocular findings could be explained by the genetic diagnosis. The molecular diagnosis for glaucoma included two cases with compound heterozygous or homozygous pathogenic alleles in CYP1B1 and one family with a dominant pathogenic variant in FOXC1; the second genetic diagnosis for the additional systemic features included compound heterozygous mutations in NPHS1 in one family and a heterozygous 18q23 deletion in another pedigree. These findings show the power of WES in the analysis of complex conditions and emphasize the importance of CYP1B1 screening in patients with congenital glaucoma regardless of the presence/absence of other systemic anomalies.

| S-EPMC5295561 | biostudies-literature

OFD1 is mutated in X-linked Joubert syndrome and interacts with LCA5-encoded lebercilin.

Project description:We ascertained a multi-generation Malaysian family with Joubert syndrome (JS). The presence of asymptomatic obligate carrier females suggested an X-linked recessive inheritance pattern. Affected males presented with mental retardation accompanied by postaxial polydactyly and retinitis pigmentosa. Brain MRIs showed the presence of a "molar tooth sign," which classifies this syndrome as classic JS with retinal involvement. Linkage analysis showed linkage to Xpter-Xp22.2 and a maximum LOD score of 2.06 for marker DXS8022. Mutation analysis revealed a frameshift mutation, p.K948NfsX8, in exon 21 of OFD1. In an isolated male with JS, a second frameshift mutation, p.E923KfsX3, in the same exon was identified. OFD1 has previously been associated with oral-facial-digital type 1 (OFD1) syndrome, a male-lethal X-linked dominant condition, and with X-linked recessive Simpson-Golabi-Behmel syndrome type 2 (SGBS2). In a yeast two-hybrid screen of a retinal cDNA library, we identified OFD1 as an interacting partner of the LCA5-encoded ciliary protein lebercilin. We show that X-linked recessive mutations in OFD1 reduce, but do not eliminate, the interaction with lebercilin, whereas X-linked dominant OFD1 mutations completely abolish binding to lebercilin. In addition, recessive mutations in OFD1 did not affect the pericentriolar localization of the recombinant protein in hTERT-RPE1 cells, whereas this localization was lost for dominant mutations. These findings offer a molecular explanation for the phenotypic spectrum observed for OFD1 mutations; this spectrum now includes OFD1 syndrome, SGBS2, and JS.

| S-EPMC2756557 | biostudies-literature

Diagnostic exome sequencing identifies GLI2 haploinsufficiency and chromosome 20 uniparental disomy in a patient with developmental anomalies.

Project description:Clinical diagnostic exome sequencing (DES) is currently infrequently used for detecting uniparental disomy (UPD). We present a patient with a dual diagnosis of GLI2 haploinsufficiency as well as UPD of chromosome 20, both identified through DES. We therefore recommend routine UPD analysis during DES to identify this genetic aberration.

| S-EPMC6028413 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data