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*604819
Table of Contents
Alternative titles; symbols
HGNC Approved Gene Symbol: PUF60
Cytogenetic location: 8q24.3 Genomic coordinates (GRCh38) : 8:143,816,344-143,829,315 (from NCBI)
The PUF60 gene encodes a splicing factor that interacts directly with SF3B4 (605593) and plays a role in the recognition of the 3-prime splice site during splicing and recruitment of U2 snRNP and subsequently U5 snRNP to the intron for splicing (summary by Dauber et al., 2013).
The far upstream element (FUSE)-binding protein (FBP, or FUBP1; 603444) binds the single-stranded FUSE of active MYC genes, possesses potent transcription activation and repression domains, and is necessary for MYC expression. Using a yeast 2-hybrid screen, Liu et al. (2000) identified a novel 60-kD protein, which they named 'FBP-interacting repressor' (FIR), that blocks activator-dependent, but not basal, transcription through TFIIH (see 189972). FIR is a 542-amino acid protein that is identical to the seven-in-absentia homolog (SIAH; 602212)-binding protein-1. Recruited through the nucleic acid-binding domain of FBP, FIR forms a ternary complex with FBP and FUSE. FIR repressed a MYC reporter via the FUSE. The N terminus of FIR contains an activator-selective repression domain capable of acting in cis or in trans in vivo and in vitro. The repression domain of FIR targets only the p89 helicase of TFIIH, which is required at several stages in transcription, but not factors required for promoter selection. Thus, FIR locks TFIIH in an activation-resistant configuration that still supports basal transcription. Northern blot analysis detected FIR expression in all tissues tested, with relatively higher levels in testis and ovary.
By database analysis, Dauber et al. (2013) mapped the PUF60 gene to chromosome 8q24.3.
Inherited mutations of the TFIIH helicase subunits XPB (133510) or XPD (278730) yield overlapping DNA repair and transcription syndromes. The high risk of cancer in these patients is not fully explained by the repair defect. The transcription defect, however, is subtle and more difficult to evaluate. Liu et al. (2001) showed that XPB and XPD mutations block transcription activation by FBP, a regulator of MYC (190080) expression, and block repression by FIR. Through TFIIH, FBP facilitates transcription until promoter escape, whereas after initiation, FIR uses TFIIH to delay promoter escape. Mutations in TFIIH that impair regulation by FBP and FIR affect proper regulation of MYC expression and have implications in the development of malignancy.
In a 21-year-old woman with Verheij syndrome (VRJS; 615583), Dauber et al. (2013) identified a de novo heterozygous missense mutation in the PUF60 gene (H169Y; 604819.0001). Studies in HeLa cells and patient cells indicated that the mutation caused a loss of function, most likely by altering the splicing pattern of PUF60.
By whole-exome sequencing in 5 patients with VRJS, El Chehadeh et al. (2017) identified heterozygous de novo mutations in the PUF60 gene (604819.0002-604819.0006), including splice site, frameshift, nonsense, and missense variants.
Low et al. (2017) identified 12 patients with VRJS who had de novo heterozygous mutations in the PUF60 gene. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, included 4 frameshift mutations resulting in premature stop codons, 3 missense mutations that clustered within the RNA recognition motif, and 5 essential splice site mutations. Analysis of cDNA from a fibroblast cell line from one of the patients with a splice site mutations confirmed aberrant splicing.
Using next-generation sequencing of a custom panel of genes involved in intellectual disability, autism spectrum disorders, and other disorders, Santos-Simarro et al. (2017) identified 3 patients with VRJS who had de novo heterozygous mutations in the PUF60 gene (see, e.g., E18K, 604819.0007). All of the mutations were confirmed by Sanger sequencing.
In a 4-year-old boy with VRJS, Graziano et al. (2017) identified de novo heterozygosity for the same E18K mutation in the PUF60 gene that had been identified by Santos-Simarro et al. (2017). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database or in an in-house database of approximately 700 control individuals, mainly of Italian origin.
Dauber et al. (2013) reported 5 unrelated children with 5 different heterozygous de novo interstitial deletions of chromosome 8q24.3 (615583); the children were identified from a cohort of patients who underwent array comparative genomic hybridization (aCGH). The deletions ranged from 78 kb to 1 Mb, and none of the breakpoints were the same. The minimal common deletion encompassed 3 genes: SCRIB (607733), NRBP2 (615563), and PUF60. Morpholino knockout of these genes in zebrafish suggested that haploinsufficiency for SCRIB and PUF60 was responsible for the phenotype, whereas loss of NRBP2 was considered unlikely to contribute to the clinical features. The patients had facial dysmorphism and global growth retardation, including 3 with microcephaly; all but 1 had developmental delay. Common dysmorphic facial features included long philtrum, anteverted nares, short nose, thin upper lip, and broad nasal root. More variable features included microretrognathia, coloboma, short neck, preauricular pits, and bitemporal narrowing. All but 1 patient had renal abnormalities, including unilateral renal agenesis, renal hypoplasia, polycystic kidneys, and ectopic renal fusion. Three patients had vertebral abnormalities, such as sacral dysplasia, coccyx agenesis, vertebral fusion, or hemivertebrae, and 4 had joint laxity or hip dislocation. Two patients had cardiac ventricular defects.
In humans, the PUF60 and SCRIB (607733) genes map to a region of chromosome 8q24.3 subject to copy number variation associated with coloboma, microcephaly, developmental delay, short stature, and craniofacial, cardiac, and renal defects (615583). Dauber et al. (2013) found that morpholino-mediated knockdown of either Puf60 or Scrib in zebrafish recapitulated some of these phenotypes, including reduced body length, microcephaly, and retrognathia. Knockdown of Puf60, but not Scrib, also resulted in heart edema. Knockdown of both genes exacerbated the short stature phenotype.
In a 21-year-old woman with Verheij syndrome (VRJS; 615583), Dauber et al. (2013) identified a de novo heterozygous c.505C-T transition in the PUF60 gene, resulting in a his169-to-tyr (H169Y) substitution at a highly conserved residue. The mutation was found by exome sequencing and was not present in the 1000 Genomes Project or Exome Variant Server databases, or in internal controls. Knockdown of PUF60 in HeLa cells led to significant changes in the splicing profile of several PUF60 target genes, which could be rescued by wildtype PUF60, but not by H169Y mutant PUF60. Similar splicing abnormalities were found in the patient's cells and in cells from patients with deletions of the PUF60 gene. In addition, the splicing of PUF60 itself was altered, resulting in less of the long isoform of PUF60. In zebrafish, wildtype PUF60 and mutant H169Y on the long isoform were able to rescue the knockout phenotype of reduced body length, but mutant H169Y on the short isoform was unable to rescue the phenotype. These findings indicated that the mutation caused a loss of function, most likely by altering the splicing pattern of PUF60.
In a 3-year-old girl (patient 1) with Verheij syndrome (VRJS; 6155830), El Chehadeh et al. (2017) identified a de novo heterozygous mutation (c.24+1G-C, NM_078480.2) in the PUF60 gene, resulting in disruption of the donor splice site for exon 1, predicted to result in skipping of exon 1. The patient had typical facial findings of Verheij syndrome and eye anomalies, including iridoretinal coloboma, bilateral microphthalmia, and optic nerve hypoplasia. The variant was not present in the ExAC database.
In a 17-year-old boy (patient 4) with Verheij syndrome (VRJS; 6155830), El Chehadeh et al. (2017) identified a de novo heterozygous 4-bp deletion (c.407_410delTCTA, NM_078480.2) in the PUF60 gene, resulting in a frameshift and a premature termination codon (Ile136ThrfsTer31). The variant was absent from the dbSNP (build 142), Exome Variant Server, and ExAC databases (June 2016).
In a 14-year-old boy (patient 2) with Verheij syndrome (VRJS; 6155830), El Chehadeh et al. (2017) identified a de novo heterozygous C-T transition (c.1342C-T, NM_078480.2) in exon 11 in the PUF60 gene, resulting in an arg448-to-ter (R448X) substitution and loss of the RRM3 domain. The variant was absent from the dbSNP (build 142), Exome Variant Server, and ExAC databases accessed June 2016.
By whole-exome sequencing in a 12-year-old girl (patient 5) with Verheij syndrome (VRJS; 6155830), El Chehadeh et al. (2017) identified a de novo heterozygous c.901A-T transversion (c.901A-T, NM_078480.2) in the PUF60 gene, leading to a lys301-to-ter (K301X) substitution. The variant was not found in the ExAC database.
In a 7-year-old boy (patient 3) with Verheij syndrome (VFJS; 6155830), El Chehadeh et al. (2017) identified a de novo heterozygous c.1448T-C transition (c.1448T-C, NM_078489.2) in the PUF60 gene, resulting in a val483-to-ala (V483A) substitution. The variant was absent from the dbSNP (build 142), Exome Variant Server, and ExAC databases accessed June 2016.
In a patient with Verheij syndrome (VRJS; 615583), Santos-Simarro et al. (2017) identified a de novo heterozygous c.541G-A transition (c.541G-A, NM_078480.2) in the PUF60 gene, resulting in a glu181-to-lys (E181K) substitution.
By whole-exome sequencing in a 4-year-old boy with VRJS, Graziano et al. (2017) identified de novo heterozygosity for the E181K mutation.
Dauber, A., Golzio, C., Guenot, C., Jodelka, F. M., Kibaek, M., Kjaergaard, S., Leheup, B., Martinet, D., Nowaczyk, M. J. M., Rosenfeld, J. A., Zeesman, S., Zunich, J., Beckmann, J. S., Hirschhorn, J. N., Hastings, M. L., Jacquemont, S., Katsanis, N. SCRIB and PUF60 are primary drivers of the multisystemic phenotypes of the 8q24.3 copy-number variant. Am. J. Hum. Genet. 93: 798-811, 2013. Note: Erratum: Am. J. Hum. Genet. 93: 994 only, 2013. [PubMed: 24140112, images, related citations] [Full Text]
El Chehadeh, S., Kerstjens-Frederikse, W. S., Thevenon, J., Kuentz, P., Bruel, A.-L., Thauvin-Robinet, C., Bensignor, C., Dollfus, H., Laugel, V., Riviere, J.-B., Duffourd, Y., Bonnet, C., and 19 others. Dominant variants in the splicing factor PUF60 cause a recognizable syndrome with intellectual disability, heart defects and short stature. Europ. J. Hum. Genet. 25: 43-51, 2017.
Graziano, C., Gusson, E., Severi, G., Isidori, F., Wischmeijer, A., Brugnara, M., Seri, M., Rossi, C. A de novo PUF60 mutation in a child with a syndromic form of coloboma and persistent fetal vasculature. Ophthal. Genet. 38: 590-592, 2017. [PubMed: 28471317, related citations] [Full Text]
Liu, J., Akoulitchev, S., Weber, A., Ge, H., Chuikov, S., Libutti, D., Wang, X. W., Conaway, J. W., Harris, C. C., Conaway, R. C., Reinberg, D., Levens, D. Defective interplay of activators and repressors with TFIIH in xeroderma pigmentosum. Cell 104: 353-363, 2001. [PubMed: 11239393, related citations] [Full Text]
Liu, J., He, L., Collins, I., Ge, H., Libutti, D., Li, J., Egly, J.-M., Levens, D. The FBP interacting repressor targets TFIIH to inhibit activated transcription. Molec. Cell 5: 331-341, 2000. [PubMed: 10882074, related citations] [Full Text]
Low, K. J., Ansari, M., Abou Jamra, R., Clarke, A., El Chehadeh, S., FitzPatrick, D. R., Greenslade, M., Henderson, A., Hurst, J., Keller, K., Kuentz, P., Prescott, T., and 12 others. PUF60 variants cause a syndrome of ID, short stature, microcephaly, coloboma, craniofacial, cardiac, renal and spinal features. Europ. J. Hum. Genet. 25: 552-559, 2017. [PubMed: 28327570, related citations] [Full Text]
Santos-Simarro, F., Vallespin, E., del Pozo, A., Ibanez, K., Silla, J. C., Fernandez, L., Nevado, J., Gonzalez-Pecellin, H., Montano, V. E. F., Martin, R., Alba Valdivia, L. I., Garcia-Minaur, S., Lapunzina, P., Palomares-Bralo, M. Eye coloboma and complex cardiac malformations belong to the clinical spectrum of PUF60 variants. (Letter) Clin. Genet. 92: 350-351, 2017. [PubMed: 28074499, related citations] [Full Text]
Alternative titles; symbols
HGNC Approved Gene Symbol: PUF60
SNOMEDCT: 1229895008;
Cytogenetic location: 8q24.3 Genomic coordinates (GRCh38) : 8:143,816,344-143,829,315 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 8q24.3 | Verheij syndrome | 615583 | Autosomal dominant | 3 |
The PUF60 gene encodes a splicing factor that interacts directly with SF3B4 (605593) and plays a role in the recognition of the 3-prime splice site during splicing and recruitment of U2 snRNP and subsequently U5 snRNP to the intron for splicing (summary by Dauber et al., 2013).
The far upstream element (FUSE)-binding protein (FBP, or FUBP1; 603444) binds the single-stranded FUSE of active MYC genes, possesses potent transcription activation and repression domains, and is necessary for MYC expression. Using a yeast 2-hybrid screen, Liu et al. (2000) identified a novel 60-kD protein, which they named 'FBP-interacting repressor' (FIR), that blocks activator-dependent, but not basal, transcription through TFIIH (see 189972). FIR is a 542-amino acid protein that is identical to the seven-in-absentia homolog (SIAH; 602212)-binding protein-1. Recruited through the nucleic acid-binding domain of FBP, FIR forms a ternary complex with FBP and FUSE. FIR repressed a MYC reporter via the FUSE. The N terminus of FIR contains an activator-selective repression domain capable of acting in cis or in trans in vivo and in vitro. The repression domain of FIR targets only the p89 helicase of TFIIH, which is required at several stages in transcription, but not factors required for promoter selection. Thus, FIR locks TFIIH in an activation-resistant configuration that still supports basal transcription. Northern blot analysis detected FIR expression in all tissues tested, with relatively higher levels in testis and ovary.
By database analysis, Dauber et al. (2013) mapped the PUF60 gene to chromosome 8q24.3.
Inherited mutations of the TFIIH helicase subunits XPB (133510) or XPD (278730) yield overlapping DNA repair and transcription syndromes. The high risk of cancer in these patients is not fully explained by the repair defect. The transcription defect, however, is subtle and more difficult to evaluate. Liu et al. (2001) showed that XPB and XPD mutations block transcription activation by FBP, a regulator of MYC (190080) expression, and block repression by FIR. Through TFIIH, FBP facilitates transcription until promoter escape, whereas after initiation, FIR uses TFIIH to delay promoter escape. Mutations in TFIIH that impair regulation by FBP and FIR affect proper regulation of MYC expression and have implications in the development of malignancy.
In a 21-year-old woman with Verheij syndrome (VRJS; 615583), Dauber et al. (2013) identified a de novo heterozygous missense mutation in the PUF60 gene (H169Y; 604819.0001). Studies in HeLa cells and patient cells indicated that the mutation caused a loss of function, most likely by altering the splicing pattern of PUF60.
By whole-exome sequencing in 5 patients with VRJS, El Chehadeh et al. (2017) identified heterozygous de novo mutations in the PUF60 gene (604819.0002-604819.0006), including splice site, frameshift, nonsense, and missense variants.
Low et al. (2017) identified 12 patients with VRJS who had de novo heterozygous mutations in the PUF60 gene. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, included 4 frameshift mutations resulting in premature stop codons, 3 missense mutations that clustered within the RNA recognition motif, and 5 essential splice site mutations. Analysis of cDNA from a fibroblast cell line from one of the patients with a splice site mutations confirmed aberrant splicing.
Using next-generation sequencing of a custom panel of genes involved in intellectual disability, autism spectrum disorders, and other disorders, Santos-Simarro et al. (2017) identified 3 patients with VRJS who had de novo heterozygous mutations in the PUF60 gene (see, e.g., E18K, 604819.0007). All of the mutations were confirmed by Sanger sequencing.
In a 4-year-old boy with VRJS, Graziano et al. (2017) identified de novo heterozygosity for the same E18K mutation in the PUF60 gene that had been identified by Santos-Simarro et al. (2017). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database or in an in-house database of approximately 700 control individuals, mainly of Italian origin.
Dauber et al. (2013) reported 5 unrelated children with 5 different heterozygous de novo interstitial deletions of chromosome 8q24.3 (615583); the children were identified from a cohort of patients who underwent array comparative genomic hybridization (aCGH). The deletions ranged from 78 kb to 1 Mb, and none of the breakpoints were the same. The minimal common deletion encompassed 3 genes: SCRIB (607733), NRBP2 (615563), and PUF60. Morpholino knockout of these genes in zebrafish suggested that haploinsufficiency for SCRIB and PUF60 was responsible for the phenotype, whereas loss of NRBP2 was considered unlikely to contribute to the clinical features. The patients had facial dysmorphism and global growth retardation, including 3 with microcephaly; all but 1 had developmental delay. Common dysmorphic facial features included long philtrum, anteverted nares, short nose, thin upper lip, and broad nasal root. More variable features included microretrognathia, coloboma, short neck, preauricular pits, and bitemporal narrowing. All but 1 patient had renal abnormalities, including unilateral renal agenesis, renal hypoplasia, polycystic kidneys, and ectopic renal fusion. Three patients had vertebral abnormalities, such as sacral dysplasia, coccyx agenesis, vertebral fusion, or hemivertebrae, and 4 had joint laxity or hip dislocation. Two patients had cardiac ventricular defects.
In humans, the PUF60 and SCRIB (607733) genes map to a region of chromosome 8q24.3 subject to copy number variation associated with coloboma, microcephaly, developmental delay, short stature, and craniofacial, cardiac, and renal defects (615583). Dauber et al. (2013) found that morpholino-mediated knockdown of either Puf60 or Scrib in zebrafish recapitulated some of these phenotypes, including reduced body length, microcephaly, and retrognathia. Knockdown of Puf60, but not Scrib, also resulted in heart edema. Knockdown of both genes exacerbated the short stature phenotype.
In a 21-year-old woman with Verheij syndrome (VRJS; 615583), Dauber et al. (2013) identified a de novo heterozygous c.505C-T transition in the PUF60 gene, resulting in a his169-to-tyr (H169Y) substitution at a highly conserved residue. The mutation was found by exome sequencing and was not present in the 1000 Genomes Project or Exome Variant Server databases, or in internal controls. Knockdown of PUF60 in HeLa cells led to significant changes in the splicing profile of several PUF60 target genes, which could be rescued by wildtype PUF60, but not by H169Y mutant PUF60. Similar splicing abnormalities were found in the patient's cells and in cells from patients with deletions of the PUF60 gene. In addition, the splicing of PUF60 itself was altered, resulting in less of the long isoform of PUF60. In zebrafish, wildtype PUF60 and mutant H169Y on the long isoform were able to rescue the knockout phenotype of reduced body length, but mutant H169Y on the short isoform was unable to rescue the phenotype. These findings indicated that the mutation caused a loss of function, most likely by altering the splicing pattern of PUF60.
In a 3-year-old girl (patient 1) with Verheij syndrome (VRJS; 6155830), El Chehadeh et al. (2017) identified a de novo heterozygous mutation (c.24+1G-C, NM_078480.2) in the PUF60 gene, resulting in disruption of the donor splice site for exon 1, predicted to result in skipping of exon 1. The patient had typical facial findings of Verheij syndrome and eye anomalies, including iridoretinal coloboma, bilateral microphthalmia, and optic nerve hypoplasia. The variant was not present in the ExAC database.
In a 17-year-old boy (patient 4) with Verheij syndrome (VRJS; 6155830), El Chehadeh et al. (2017) identified a de novo heterozygous 4-bp deletion (c.407_410delTCTA, NM_078480.2) in the PUF60 gene, resulting in a frameshift and a premature termination codon (Ile136ThrfsTer31). The variant was absent from the dbSNP (build 142), Exome Variant Server, and ExAC databases (June 2016).
In a 14-year-old boy (patient 2) with Verheij syndrome (VRJS; 6155830), El Chehadeh et al. (2017) identified a de novo heterozygous C-T transition (c.1342C-T, NM_078480.2) in exon 11 in the PUF60 gene, resulting in an arg448-to-ter (R448X) substitution and loss of the RRM3 domain. The variant was absent from the dbSNP (build 142), Exome Variant Server, and ExAC databases accessed June 2016.
By whole-exome sequencing in a 12-year-old girl (patient 5) with Verheij syndrome (VRJS; 6155830), El Chehadeh et al. (2017) identified a de novo heterozygous c.901A-T transversion (c.901A-T, NM_078480.2) in the PUF60 gene, leading to a lys301-to-ter (K301X) substitution. The variant was not found in the ExAC database.
In a 7-year-old boy (patient 3) with Verheij syndrome (VFJS; 6155830), El Chehadeh et al. (2017) identified a de novo heterozygous c.1448T-C transition (c.1448T-C, NM_078489.2) in the PUF60 gene, resulting in a val483-to-ala (V483A) substitution. The variant was absent from the dbSNP (build 142), Exome Variant Server, and ExAC databases accessed June 2016.
In a patient with Verheij syndrome (VRJS; 615583), Santos-Simarro et al. (2017) identified a de novo heterozygous c.541G-A transition (c.541G-A, NM_078480.2) in the PUF60 gene, resulting in a glu181-to-lys (E181K) substitution.
By whole-exome sequencing in a 4-year-old boy with VRJS, Graziano et al. (2017) identified de novo heterozygosity for the E181K mutation.
Dauber, A., Golzio, C., Guenot, C., Jodelka, F. M., Kibaek, M., Kjaergaard, S., Leheup, B., Martinet, D., Nowaczyk, M. J. M., Rosenfeld, J. A., Zeesman, S., Zunich, J., Beckmann, J. S., Hirschhorn, J. N., Hastings, M. L., Jacquemont, S., Katsanis, N. SCRIB and PUF60 are primary drivers of the multisystemic phenotypes of the 8q24.3 copy-number variant. Am. J. Hum. Genet. 93: 798-811, 2013. Note: Erratum: Am. J. Hum. Genet. 93: 994 only, 2013. [PubMed: 24140112] [Full Text: https://doi.org/10.1016/j.ajhg.2013.09.010]
El Chehadeh, S., Kerstjens-Frederikse, W. S., Thevenon, J., Kuentz, P., Bruel, A.-L., Thauvin-Robinet, C., Bensignor, C., Dollfus, H., Laugel, V., Riviere, J.-B., Duffourd, Y., Bonnet, C., and 19 others. Dominant variants in the splicing factor PUF60 cause a recognizable syndrome with intellectual disability, heart defects and short stature. Europ. J. Hum. Genet. 25: 43-51, 2017.
Graziano, C., Gusson, E., Severi, G., Isidori, F., Wischmeijer, A., Brugnara, M., Seri, M., Rossi, C. A de novo PUF60 mutation in a child with a syndromic form of coloboma and persistent fetal vasculature. Ophthal. Genet. 38: 590-592, 2017. [PubMed: 28471317] [Full Text: https://doi.org/10.1080/13816810.2017.1318927]
Liu, J., Akoulitchev, S., Weber, A., Ge, H., Chuikov, S., Libutti, D., Wang, X. W., Conaway, J. W., Harris, C. C., Conaway, R. C., Reinberg, D., Levens, D. Defective interplay of activators and repressors with TFIIH in xeroderma pigmentosum. Cell 104: 353-363, 2001. [PubMed: 11239393] [Full Text: https://doi.org/10.1016/s0092-8674(01)00223-9]
Liu, J., He, L., Collins, I., Ge, H., Libutti, D., Li, J., Egly, J.-M., Levens, D. The FBP interacting repressor targets TFIIH to inhibit activated transcription. Molec. Cell 5: 331-341, 2000. [PubMed: 10882074] [Full Text: https://doi.org/10.1016/s1097-2765(00)80428-1]
Low, K. J., Ansari, M., Abou Jamra, R., Clarke, A., El Chehadeh, S., FitzPatrick, D. R., Greenslade, M., Henderson, A., Hurst, J., Keller, K., Kuentz, P., Prescott, T., and 12 others. PUF60 variants cause a syndrome of ID, short stature, microcephaly, coloboma, craniofacial, cardiac, renal and spinal features. Europ. J. Hum. Genet. 25: 552-559, 2017. [PubMed: 28327570] [Full Text: https://doi.org/10.1038/ejhg.2017.27]
Santos-Simarro, F., Vallespin, E., del Pozo, A., Ibanez, K., Silla, J. C., Fernandez, L., Nevado, J., Gonzalez-Pecellin, H., Montano, V. E. F., Martin, R., Alba Valdivia, L. I., Garcia-Minaur, S., Lapunzina, P., Palomares-Bralo, M. Eye coloboma and complex cardiac malformations belong to the clinical spectrum of PUF60 variants. (Letter) Clin. Genet. 92: 350-351, 2017. [PubMed: 28074499] [Full Text: https://doi.org/10.1111/cge.12965]
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