New mutations and an updated database for the patched‐1 (<i><scp>PTCH</scp>1</i>) gene

Reinders, Marie G H C; Hout, Antonius F. van; Cosgun, B.; Paulussen, Aimée D C; Leter, Edward M; Steijlen, P.M.; Mosterd, Klara; Geel, Michel van; Gille, Johan J. P.

doi:10.1002/mgg3.380

Cited by 27 publications

(27 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…HGMD and ClinVar databases were used to identify if pathogenic mutations were previously reported in the literature, and data were extracted on 10 January 2017. The more recently updated PTCH1 Leiden Open Variation Database (LOVD) in 2018 was not available for inclusion in our primary analysis (Reinders et al, ), although novel variants were checked for presence in this database and none were present. ClinVar was restricted to the 17 laboratories that met the minimum requirements for data sharing and quality assurance (ClinGen, ), and HGMD was restricted to DM.…”

Section: Methodsmentioning

confidence: 99%

Whole‐exome sequencing of nevoid basal cell carcinoma syndrome families and review of Human Gene Mutation Database PTCH1 mutation data

Gianferante

Rotunno

Dean

et al. 2018

Molec Gen & Gen Med

View full text Add to dashboard Cite

BackgroundNevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder with variable expression and nearly complete penetrance. PTCH1 is the major susceptibility locus and has no known hot spots or genotype–phenotype relationships.MethodsWe evaluated 18 NBCCS National Cancer Institute (NCI) families plus PTCH1 data on 333 NBCCS disease‐causing mutations (DM) reported in the Human Gene Mutation Database (HGMD). National Cancer Institute families underwent comprehensive genomic evaluation, and clinical data were extracted from NCI and HGMD cases. Genotype–phenotype relationships were analyzed using Fisher's exact tests focusing on mutation type and PTCH1 domains.Results PTCH1 pathogenic mutations were identified in 16 of 18 NCI families, including three previously mutation‐negative families. PTCH1 mutations were spread across the gene with no hot spot. After adjustment for multiple tests, a statistically significant genotype–phenotype association was observed for developmental delay and gross deletion–insertions (p = 9.0 × 10−6), and suggestive associations between falx cerebri calcification and all transmembrane domains (p = 0.002) and severe outcomes and gross deletion–insertions (p = 4.0 × 10−4).ConclusionOverall, 89% of our NCI families had a pathogenic PTCH1 mutation. The identification of PTCH1 mutations in previously mutation‐negative families underscores the importance of repeated testing when new technologies become available. Additional clinical information linked to mutation databases would enhance follow‐up and future studies of genotype–phenotype relationships.

show abstract

Section: Methodsmentioning

confidence: 99%

Whole‐exome sequencing of nevoid basal cell carcinoma syndrome families and review of Human Gene Mutation Database PTCH1 mutation data

Gianferante

Rotunno

Dean

et al. 2018

Molec Gen & Gen Med

View full text Add to dashboard Cite

show abstract

“…Several hundred pathogenic variants in the PTCH1 gene have been described [6,7]. The novel de novo heterozygous variant c.2834delGinsAGATGTTGTGGACCC, p. Arg945GlnfsTer22, in our patient causes truncation of one of the extracellular loops of the PTCH1 leading to the loss of a significant part of the C-terminal protein, including five transmembrane domains [6].…”

Section: Discussionmentioning

confidence: 74%

“…Megalencephaly is defined as an oversized brain with head circumference exceeding the age-related mean by two or more standard deviations [9]. A tendency to megalencephaly has been reported in both FOXP1-and PTCH1related conditions [3][4][5][7][8][9]. We describe here a girl with co-occurrence of heterozygous disease-causing variants in both FOXP1 and PTCH1 genes in association with extreme megalencephaly, unreported in mutations of either gene, dysmorphic features, abnormal corpus callosum, and profound intellectual disability.…”

Section: Introductionmentioning

confidence: 89%

“…The PTCH1 (patched homologue 1, OMIM 601309) gene on chromosome 9q22.3 encodes a transmembrane glycoprotein [6] which functions as a hedgehog (HH) receptor and regulates HH signalling at the primary cilium [6,7]. Heterozygous germline PTCH1 pathogenic variants cause Gorlin syndrome (OMIM 109400), an autosomal dominant disorder that predisposes affected individuals to developmental defects and tumourigenesis [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Co-occurrence of mutations in FOXP1 and PTCH1 in a girl with extreme megalencephaly, callosal dysgenesis and profound intellectual disability

et al. 2018

View full text Add to dashboard Cite

Heterozygous disruptions in FOXP1 are responsible for developmental delay, intellectual disability and speech deficit. Heterozygous germline PTCH1 disease-causing variants cause Gorlin syndrome. We describe a girl with extreme megalencephaly, developmental delay and severe intellectual disability. Dysmorphic features included prominent forehead, frontal hair upsweep, flat, wide nasal bridge, low-set, abnormally modelled ears and post-axial cutaneous appendages on the hands. Brain MRI showed partial agenesis of the corpus callosum and widely separated leaves of the septum pellucidum. Exome sequencing of a gene set representing a total of 4813 genes with known relationships to human diseases revealed an already known heterozygous de novo nonsense disease-causing variant in FOXP1 (c.1573C>T, p.Arg525Ter) and a heterozygous novel de novo frameshift nonsense variant in PTCH1 (c.2834delGinsAGATGTTGTGGACCC, p.Arg945GlnfsTer22). The composite phenotype of the patient seems to be the result of two monogenic diseases, although more severe than described in conditions due to disease-causing variants in either gene.

show abstract

“…Hedgehog (Hh) signaling pathway played a central role in promoting the cellular processes and activities [102], and the aberrant activation of Hh signaling led to various types of cancer and defects in the organism cells [103]. The Ptc1 protein of cAMP signaling pathway could maintain the Hh pathway in an inactive state by inhibiting translocation of the signaling effector Smoothened (Smo) [104–105]. In this paper, the CNGCB1 (K04952) and Ptc1 (K06225) were detected as the major two parts KOs of the annotated components in cAMP signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the transcriptome data in Litopenaeus vannamei reveals the immune basis and predicts the hub regulation-genes in response to high-pH stress

Huang

Cheng

et al. 2018

PLoS ONE

View full text Add to dashboard Cite

Soil salinization erodes the farmlands and poses a serious threat to human life, reuse of the saline-alkali lands as cultivated resources becomes increasingly prominent. Pacific white shrimp (Litopenaeus vannamei) is an important farmed aquatic species for the development and utilization of the saline-alkali areas. However, little is known about the adaptation mechanism of this species in terms of high-pH stress. In the present study, a transcriptome analysis on the gill tissues of L. vannamei in response to high-pH stress (pH 9.3 ± 0.1) was conducted. After analyzing, the cyclic nucleotide gated channel-Ca2+ (CNGC-Ca2+) and patched 1 (Ptc1) were detected as the majority annotated components in the cAMP signaling pathway (KO04024), indicating that the CNGC-Ca2+ and Ptc1 might be the candidate components for transducing and maintaining the high-pH stress signals, respectively. The immunoglobulin superfamily (IgSF), heat shock protein (HSP), glutathione s-transferase (GST), prophenoloxidase/phenoloxidase (proPO/PO), superoxide dismutase (SOD), anti-lipopolysaccharide factor (ALF) and lipoprotein were discovered as the major transcribed immune factors in response to high-pH stress. To further detect hub regulation-genes, protein-protein interaction (PPI) networks were constructed; the genes/proteins “Polymerase (RNA) II (DNA directed) polypeptide A” (POLR2A), “Histone acetyltransferase p300” (EP300) and “Heat shock 70kDa protein 8” (HSPA8) were suggested as the top three hub regulation-genes in response to acute high-pH stress; the genes/proteins “Heat shock 70kDa protein 4” (HSPA4), “FBJ murine osteosarcoma viral oncogene homolog” (FOS) and “Nucleoporin 54kDa” (NUP54) were proposed as the top three hub regulation-genes involved in adapting endurance high-pH stress; the protein-interactions of “EP300-HSPA8” and “HSPA4-NUP54” were detected as the most important biological interactions in response to the high-pH stress; and the HSP70 family genes might play essential roles in the adaptation of the high-pH stress environment in L. vannamei. These findings provide the first insight into the molecular and immune basis of L. vannamei in terms of high-pH environments, and the construction of a PPI network might improve our understanding in revealing the hub regulation-genes in response to abiotic stress in shrimp species and might be beneficial for further studies.

show abstract

New mutations and an updated database for the patched‐1 (PTCH1) gene

Cited by 27 publications

References 20 publications

Whole‐exome sequencing of nevoid basal cell carcinoma syndrome families and review of Human Gene Mutation Database PTCH1 mutation data

Whole‐exome sequencing of nevoid basal cell carcinoma syndrome families and review of Human Gene Mutation Database PTCH1 mutation data

Co-occurrence of mutations in FOXP1 and PTCH1 in a girl with extreme megalencephaly, callosal dysgenesis and profound intellectual disability

Analysis of the transcriptome data in Litopenaeus vannamei reveals the immune basis and predicts the hub regulation-genes in response to high-pH stress

Contact Info

Product

Resources

About