Alternative titles; symbols
HGNC Approved Gene Symbol: MAGEL2
SNOMEDCT: 1229946007;
Cytogenetic location: 15q11.2 Genomic coordinates (GRCh38): 15:23,643,549-23,647,867 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 15q11.2 | Schaaf-Yang syndrome | 615547 | Autosomal dominant | 3 |
The MAGEL2 gene encodes a ubiquitin ligase enhancer that is required for endosomal protein recycling (summary by Schaaf et al., 2013).
Boccaccio et al. (1999) reported the characterization of the MAGEL2 (MAGE-like-2) gene, which they identified within the critical region for Prader-Willi syndrome (PWS; 176270). By RT-PCR analysis of fibroblast and total brain RNA from normal individuals and patients with Angelman (105830) and Prader-Willi syndromes, they demonstrated that MAGEL2 is transcribed only from the paternal allele.
Lee et al. (2000) independently cloned and characterized the MAGEL2 gene, also known as NDNL1 (necdin-like-1). The MAGEL2 gene encodes a 529-amino acid protein with 51% sequence similarity to necdin (NDN; 602117). As shown by Northern blot analysis, the 4.5-kb MAGEL2 transcript is expressed predominantly in brain, the primary tissue affected in PWS, and in several fetal tissues. MAGEL2 is imprinted with monoallelic expression in control brain, and with paternal-only expression in the central nervous system, as demonstrated by its lack of expression in brain from a PWS-affected individual. The orthologous mouse gene, Magel2, is imprinted with paternal-only expression and is expressed predominantly in late developmental stages and adult brain as shown by Northern blot analysis, RT-PCR, and whole-mount RNA in situ hybridization. Magel2 distribution partially overlaps that of Ndn, with strong expression being detected in the central nervous system in midgestation mouse embryos by in situ hybridization. Lee et al. (2000) hypothesized that, although loss of necdin expression may be important in the neonatal presentation of PWS, loss of MAGEL2 may be critical to abnormalities in brain development and dysmorphic features in individuals with PWS.
Lee et al. (2005) demonstrated that necdin and Magel2 bound to and prevented proteasomal degradation of Fez1 (604825), which is implicated in axonal outgrowth and kinesin-mediated transport, and also bound to BBS4 (600374) protein in cotransfected cells. The interactions among necdin, Magel2, Fez1, and BBS4 occurred at or near centrosomes. Centrosomal or pericentriolar dysfunction has previously been implicated in BBS (209900) and may also be important in features of PWS that overlap with BBS, such as learning disabilities, hypogonadism, and obesity.
Boccaccio et al. (1999) determined that the MAGEL2 gene is intronless.
Boccaccio et al. (1999) identified the MAGEL2 gene within the PWS deletion region on chromosome 15q11-q13. The mouse Magel2 gene resides on chromosome 7C, within a region of conserved synteny with human 15q11-q13.
Lee et al. (2000) determined that the MAGEL2 gene is located 41 kb distal to the necdin gene (NDN; 602117). The mouse Magel2 gene is located within 150 kb of Ndn.
In 4 unrelated boys with Schaaf-Yang syndrome (SHFYNG; 615547), Schaaf et al. (2013) identified 4 different de novo heterozygous truncating mutations in the MAGEL2 gene (605283.0001-605283.0004). All mutations occurred on the paternal allele. Because the maternal allele is not normally expressed, the findings were consistent with a loss of MAGEL2 function. The mutation in the first patient was found by clinical whole-exome sequencing. Based on these results, a research database of 1,248 whole-exome sequencing cases were reviewed, and the 3 remaining cases were identified.
In 2 sisters with Schaaf-Yang syndrome, Soden et al. (2014) identified a heterozygous truncating mutation in the MAGEL2 gene (c.1996dupC; 605283.0005). The mutation was found by whole-genome sequencing and apparently resulted from gonadal mosaicism; the mutation was missed by initial whole-exome sequencing. The patients were part of a larger cohort of 100 families with neurodevelopmental disorders who underwent whole-exome or whole-genome sequencing.
In 3 fetuses, born of unrelated parents, with Schaaf-Yang syndrome manifest as arthrogryposis multiplex congenita (AMC) and death in utero, Mejlachowicz et al. (2015) identified a heterozygous truncating mutation in the MAGEL2 gene (c.1996delC; 605283.0006). The mutation, which was found by a combination of linkage analysis and whole-exome sequencing and confirmed by Sanger sequencing, was inherited from the unaffected father who inherited it from his unaffected mother. Direct Sanger sequencing of the MAGEL2 gene in 84 additional cases of AMC and/or decreased fetal motility identified another patient with a de novo heterozygous truncating mutation (c.2118delT; 605283.0007) that occurred on the paternal allele. This patient had severe hypotonia with respiratory distress and died at 2 days of age.
In 18 patients with SHFYNG, Fountain et al. (2017) identified heterozygous truncating mutations in the MAGEL2 gene (see, e.g., 605283.0005-605383.0006, 605283.0008-605283.0009). The patients were ascertained based on genotype from whole-exome or direct Sanger sequencing through multiple research-based centers or laboratories. All mutations, which were confirmed by Sanger sequencing, resulted in a truncated protein. All patients tested carried the mutation on the paternal allele, consistent with maternal imprinting of the MAGEL2 gene. In 3 families, the mutation segregated with the disorder: unaffected fathers inherited the mutation from an unaffected mother. Fountain et al. (2017) speculated that the mutations could result in a dominant-negative effect. The phenotype was highly variable, ranging from relatively mild contractures to fetal akinesia, AMC, and early death. Nucleotides c.1990-1996 include a sequence of 7 cytosines that represent a mutational hotspot: 11 individuals from 7 families had a c.1996dupC mutation (605283.0005), and 2 from the same family had a c.1996delC mutation (605283.0006). Functional studies of the variants and studies of patient cells were not performed.
Jobling et al. (2018) reported 5 patients from 3 unrelated families who were diagnosed clinically with Chitayat-Hall syndrome but were found to carry heterozygous loss-of-function mutations in the MAGEL2 gene on the paternal allele (see, e.g., 605283.0005). One of the patients was the affected sister originally reported by Chitayat et al. (1990), who was heterozygous for a complex rearrangement and partial deletion of MAGEL2.
In 5 unrelated patients with SHFYNG, Patak et al. (2019) identified heterozygous mutations in the MAGEL2 gene. The mutations were found by whole-exome sequencing and the patients were ascertained through collaborative efforts. Four patients carried frameshift or nonsense mutations, including c.1996delC, and 1 (patient 2) carried a missense variant (A538E; 605283.0010). The mutations, all of which occurred on the paternal allele, occurred de novo in 4 patients and resulted from low-level mosaicism in an unaffected father in the fifth. Functional studies of the variants and studies of patient cells were not performed.
In a patient with Schaaf-Yang syndrome and chronic intestinal pseudoobstruction, Bayat et al. (2018) sequenced the MAGEL2 gene and identified heterozygosity for the c.1996dupC mutation in the (605283.0005) in the MAGEL2 gene.
Among 78 patients with Schaaf-Yang syndrome reported by McCarthy et al. (2018), 42 had MAGEL2 mutations within a mutation hotspot region where there are 7 cytosines at nucleotides 1990-1996. The most common mutation was c.1996dupC, found in 35 patients. The authors compared the phenotypes of 2 groups of patients with Schaaf-Yang syndrome based on the locations of their MAGEL2 mutation: 35 patients with c.1996dupC and 38 patients with any truncating mutation other than c.1996dupC. Patients with c.1996dupC had more severe disease with a higher prevalence of joint contractures, feeding difficulties, and respiratory problems, as well as more severe intellectual disability/developmental delay. Mean IQ for those with c.1996dupC was 14.2 (n = 5), while those without a c.1996dupC mutation was 53.2 (n = 8). The mutation associated with the most severe phenotype, however, was deletion of a cytosine at nucleotide 1996 (c.1996delC; 605283.0006). Among the 5 patients with this mutation reported by McCarthy et al. (2018), all died prenatally or within hours after birth.
Possible Association with Age at Menarche
Perry et al. (2014) performed a metaanalysis using genomewide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, and found robust evidence (p less than 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with 3 loci (DLK1, 176290-WDR25, 618059; MKRN3, 603856-MAGEL2; and KCNK9, 605874) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. The significant paternal parent-of-origin effect in delaying age of menarche at the MKRN3-MAGEL2 locus was associated with SNP rs12148769 (p(pat) = 2.4 x 10(-6)). It was unclear which of the genes explained this menarche signal.
Mammalian circadian rhythms of activity are generated within the suprachiasmatic nucleus (SCN). Transcripts from the imprinted, paternally expressed MAGEL2 gene, which maps to the chromosomal region associated with Prader-Willi syndrome (PWS; 176270), are highly enriched in the SCN. Kozlov et al. (2007) found that in mice the Magel2 message is circadianly expressed and peaks during the subjective day. Mice deficient in Magel2 expression entrain to light cycles and express normal running-wheel rhythms, but with markedly reduced amplitude of activity and increased daytime activity. These changes are associated with reductions in food intake and male fertility. Levels of orexin (602358) levels and orexin-positive neurons in the lateral hypothalamus are substantially reduced, suggesting that some of the consequences of Magel2 loss are mediated through changes in orexin signaling. The robust rhythmicity of Magel2 expression in the SCN and the altered behavioral rhythmicity of null mice revealed Magel2 to be a clock-controlled circadian output gene whose disruption results in some of the phenotypes characteristic of PWS.
Bischof et al. (2007) found that Magel2-null mice showed features similar to those of PWS in humans. There was reduced embryonic viability associated with loss of Magel2. Magel2-null mice showed neonatal growth retardation, excessive weight gain after weaning, and increased adiposity with altered metabolism, including increased fasting insulin and elevated cholesterol, in adulthood. Mutant mice also showed abnormalities in the circadian pattern of feeding behavior. The findings implicated loss of the Magel2 gene in hypothalamic dysfunction.
Schaller et al. (2010) reported that a Magel2-deficient mouse strain with 50% neonatal mortality had an altered onset of suckling activity and subsequent impaired feeding, suggesting a role of MAGEL2 in the suckling deficit seen in PWS newborns. The hypothalamus of Magel2 mutant neonates showed a significant reduction in oxytocin (OT; 167050). Furthermore, injection of a specific oxytocin receptor antagonist in wildtype neonates recapitulated the feeding deficiency seen in Magel2 mutants, and a single injection of oxytocin, 3 to 5 hours after birth, rescued the phenotype of Magel2 mutant pups, allowing all of them to survive. The authors proposed that oxytocin supplementation might constitute a promising treatment for feeding difficulties in PWS neonates and potentially in other newborns with impaired feeding onset.
In a 13-year-old boy with Schaaf-Yang syndrome (SHFYNG; 615547), Schaaf et al. (2013) identified a de novo heterozygous 1-bp deletion (c.1652delT, NM_019066.4) in the MAGEL2 gene, resulting in a frameshift and premature termination (Val551fs) on the paternal allele. The mutation was found by whole-exome sequencing.
In an 8-year-old boy with Schaaf-Yang syndrome (SHFYNG; 615547), Schaaf et al. (2013) identified a de novo heterozygous 1-bp deletion (c.1802delC, NM_019066.4) in the MAGEL2 gene, resulting in a frameshift and premature termination (Pro601fs) on the paternal allele. The mutation was found by whole-exome sequencing. The patient met the classic clinical criteria for Prader-Willi syndrome.
In a 5-year-old boy with Schaaf-Yang syndrome (SHFYNG; 615547), Schaaf et al. (2013) identified a de novo heterozygous 2-bp deletion (c.3181_3182delAT, NM_019066.4) in the MAGEL2 gene, resulting in a frameshift and premature termination (Ile1061fs) on the paternal allele. The mutation was found by whole-exome sequencing.
In a 19-year-old boy with Schaaf-Yang syndrome (SHFYNG; 615547), Schaaf et al. (2013) identified a de novo heterozygous c.3124C-T transition (c.3124C-T, NM_019066.4) in the MAGEL2 gene, resulting in a gln1024-to-ter (Q1024X) substitution on the paternal allele. The mutation was found by whole-exome sequencing.
In 2 sisters with Schaaf-Yang syndrome (SHFYNG; 615547), Soden et al. (2014) identified a heterozygous 1-bp duplication (c.1996dupC) in the MAGEL2 gene, predicted to result in a frameshift, premature termination (Gln666ProfsTer47), and a loss of function. The mutation, which was found by whole-genome sequencing and confirmed by Sanger sequencing, was undetectable in the parents, suggesting gonadal mosaicism of this paternally expressed gene.
Fountain et al. (2017) identified a heterozygous c.1996dupC mutation in 11 patients with SHFYNG from 7 unrelated families; in 5 of these patients the mutation occurred de novo. All of these patients were ascertained based on genotype from whole-exome or direct Sanger sequencing through multiple research-based centers or laboratories. All mutations were confirmed by Sanger sequencing.
In a patient with Schaaf-Yang syndrome, who had been clinically diagnosed with Chitayat-Hall syndrome, Jobling et al. (2018) identified heterozygosity for the c.1996dupC mutation in the MAGEL2 gene.
Among 78 patients with Schaaf-Yang syndrome reported by McCarthy et al. (2018), 35 (45%) had the c.1996dupC mutation in the MAGEL2 gene. The authors compared these patients to 38 patients with MAGEL2 mutations in other locations and found that patients with c.1996dupC had a higher prevalence of joint contractures, feeding difficulties, and respiratory problems, as well as more severe intellectual disability/developmental delay.
In a patient with Schaaf-Yang syndrome and chronic intestinal pseudoobstruction, Bayat et al. (2018) identified heterozygosity for the c.1996dupC in the MAGEL2 gene.
In 3 fetuses, born of unrelated parents, with Schaaf-Yang syndrome (SHFYNG; 615547) manifest as arthrogryposis multiplex congenita (AMC) and death in utero, Mejlachowicz et al. (2015) identified a heterozygous 1-bp deletion (c.1996delC, NM_019066.4) in the MAGEL2 gene, resulting in a frameshift and premature termination (Gln666SerfsTer36). The mutation, which was found by a combination of linkage analysis and whole-exome sequencing and confirmed by Sanger sequencing, was inherited from the unaffected father who had inherited it from his unaffected mother. The mutation was not found in the dbSNP (build 144) or Exome Sequencing Project database. Skeletal muscle derived from one of the fetuses showed markedly decreased expression of the paternal MAGEL2 allele, as well as lack of MAGEL2 expression from the maternal allele.
Fountain et al. (2017) identified a heterozygous c.1996delC mutation in the MAGEL2 gene in 2 fetal sibs (patients 5 and 6) with SHFYNG manifest as AMC. The mutation was inherited from the unaffected father who had inherited it from his unaffected mother.
Of 78 patients with Schaaf-Yang syndrome, McCarthy et al. (2018) found that 5 had the c.1996delC mutation in the MAGEL2 gene. These patients were severely affected, dying either in utero or within a few hours after birth.
In a girl, born of unrelated parents, with Schaaf-Yang syndrome (SHFYNG; 615547) manifest as arthrogryposis multiplex congenita (AMC) and resulting in death at 2 days of age, Mejlachowicz et al. (2015) identified a de novo heterozygous 1-bp deletion (c.2118delT, NM_019066.4) in the MAGEL2 gene, resulting in a frameshift and premature termination (Leu708TrpfsTer7). The mutation, which occurred on the paternal allele, was found by direct Sanger sequencing of the MAGEL2 gene in 84 cases of AMC and/or decreased fetal motility. The mutation was not found in the dbSNP (build 144) or Exome Sequencing Project databases. Marked reduction of MAGEL2 expression was observed in the affected individual.
In a 19-year-old Spanish woman (patient 7) with Schaaf-Yang syndrome (SHFYNG; 615547), Urreizti et al. (2017) identified a de novo heterozygous c.1912C-T transition in the MAGEL2 gene, resulting in a gln638-to-ter (Q638X) substitution. Thr mutation, which was found by whole-exome sequencing, occurred on the paternal chromosome.
In 1-year-old boy (patient 4) with SHFYNG, Fountain et al. (2017) identified a de novo heterozygous Q638X mutation in the MAGEL2 gene.
In a patient (patient 8) with Schaaf-Yang syndrome (SHFYNG; 615547), Fountain et al. (2017) identified a heterozygous c.1621C-T transition in the MAGEL2 gene, resulting in a gln541-to-ter (Q541X) substitution. The mutation occurred on the paternal allele.
In an 18-year-old woman (patient 2) with Schaaf-Yang syndrome (SHFYNG; 615547), Patak et al. (2019) identified a de novo heterozygous c.1613C-A transversion (c.1613C-A, NM_019066.4) in the MAGEL2 gene, resulting in an ala538-to-glu (A538E) substitution. The mutation, which was found by whole-exome sequencing, was on the paternal allele; it was not found in the ExAC or gnomAD databases. Functional studies of the variant and studies of patient cells were not performed.
Bayat, A., Bayat, M., Lozoya, R., Schaaf, C. P. Chronic intestinal pseudo-obstruction syndrome and gastrointestinal malrotation in an infant with Schaaf-Yang syndrome--expanding the phenotypic spectrum. Europ. J. Med. Genet. 61: 627-630, 2018. [PubMed: 29660409] [Full Text: https://doi.org/10.1016/j.ejmg.2018.04.007]
Bischof, J. M., Stewart, C. L., Wevrick, R. Inactivation of the mouse Magel2 gene results in growth abnormalities similar to Prader-Willi syndrome. Hum. Molec. Genet. 16: 2713-2739, 2007. [PubMed: 17728320] [Full Text: https://doi.org/10.1093/hmg/ddm225]
Boccaccio, I., Glatt-Deeley, H., Watrin, F., Roeckel, N., Lalande, M., Muscatelli, F. The human MAGEL2 gene and its mouse homologue are paternally expressed and mapped to the Prader-Willi region. Hum. Molec. Genet. 8: 2497-2505, 1999. [PubMed: 10556298] [Full Text: https://doi.org/10.1093/hmg/8.13.2497]
Chitayat, D., Hall, J. G., Couch, R. M., Phang, M. S., Baldwin, V. J. Syndrome of mental retardation, facial anomalies, hypopituitarism, and distal arthrogryposis in sibs. Am. J. Med. Genet. 37: 65-70, 1990. [PubMed: 2240046] [Full Text: https://doi.org/10.1002/ajmg.1320370116]
Fountain, M. D., Aten, E., Cho, M. T., Juusola, J., Walkiewicz, M. A., Ray, J. W., Xia, F., Yang, Y., Graham, B. H., Bacino, C. A., Potocki, L., van Haeringen, A., and 27 others. The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families. Genet. Med. 19: 45-52, 2017. Note: Erratum: Genet. Med. 18: 1066 only, 2016. [PubMed: 27195816] [Full Text: https://doi.org/10.1038/gim.2016.53]
Jobling, R., Stavropoulos, D. J., Marshall, C. R., Cytrynbaum, C., Axford, M. M., Londero, V., Moalem, S., Orr, J., Rossignol, F., Lopes, F. D., Gauthier, J., Alos, N., and 14 others. Chitayat-Hall and Schaaf-Yang syndromes: a common aetiology: expanding the phenotype of MAGEL2-related disorders. J. Med. Genet. 55: 316-321, 2018. [PubMed: 29599419] [Full Text: https://doi.org/10.1136/jmedgenet-2017-105222]
Kozlov, S. V., Bogenpohl, J. W., Howell, M. P., Wevrick, R., Panda, S., Hogenesch, J. B., Muglia, L. J., Van Gelder, R. N., Herzog, E. D., Stewart, C. L. The imprinted gene Magel2 regulates normal circadian output. Nature Genet. 39: 1266-1272, 2007. [PubMed: 17893678] [Full Text: https://doi.org/10.1038/ng2114]
Lee, S., Kozlov, S., Hernandez, L., Chamberlain, S. J., Brannan, C. I., Stewart, C. L., Wevrick, R. Expression and imprinting of MAGEL2 suggest a role in Prader-Willi syndrome and the homologous murine imprinting phenotype. Hum. Molec. Genet. 9: 1813-1819, 2000. [PubMed: 10915770] [Full Text: https://doi.org/10.1093/hmg/9.12.1813]
Lee, S., Walker, C. L., Karten, B., Kuny, S. L., Tennese, A. A., O'Neill, M. A., Wevrick, R. Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth. Hum. Molec. Genet. 14: 627-637, 2005. [PubMed: 15649943] [Full Text: https://doi.org/10.1093/hmg/ddi059]
McCarthy, J., Lupo, P. J., Kovar, E., Rech, M., Bostwick, B., Scott, D., Kraft K., Roscioli, T., Charrow, J., Schrier Vergano, S. A., Lose, E., Smiegel, R., Lacassie, Y., Schaaf, C. P. Schaaf-Yang syndrome overview: report of 78 individuals. Am. J. Med. Genet. 176A: 2564-2574, 2018. [PubMed: 30302899] [Full Text: https://doi.org/10.1002/ajmg.a.40650]
Mejlachowicz, D., Nolent, F., Maluenda, J., Ranjatoelina-Randrianaivo, H., Giuliano, F., Gut, I., Sternberg, D., Laquerriere, A., Melki, J. Truncating mutations of MAGEL2, a gene within the Prader-Willi locus, are responsible for severe arthrogryposis. Am. J. Hum. Genet. 97: 616-620, 2015. [PubMed: 26365340] [Full Text: https://doi.org/10.1016/j.ajhg.2015.08.010]
Patak, J., Gilfert, J., Byler, M., Neerukonda, V., Thiffault, I., Cross, L., Amudhavalli, S., Pacio-Miguez, M., Palomares-Bralo, M., Garcia-Minaur, S., Santos-Simarro, F., Powis, Z., Alcaraz, W., Tang, S., Jurgens, J., Barry, B., England, E., Engle, E., Hess, J., Lebel, R. R. MAGEL2-related disorders: a study and case series. Clin. Genet. 96: 493-505, 2019. [PubMed: 31397880] [Full Text: https://doi.org/10.1111/cge.13620]
Perry, J. R. B., Day, F., Elks, C. E., Sulem, P., Thompson, D. J., Ferreira, T., He, C., Chasman, D. I., Esko, T., Thorleifsson, G., Albrecht, E., Ang, W. Q., and 192 others. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. Nature 514: 92-97, 2014. [PubMed: 25231870] [Full Text: https://doi.org/10.1038/nature13545]
Schaaf, C. P., Gonzalez-Garay, M. L., Xia, F., Potocki, L., Gripp, K. W., Zhang, B., Peters, B. A., McElwain, M. A., Drmanac, R., Beaudet, A. L., Caskey, C. T., Yang, Y. Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism. Nature Genet. 45: 1405-1408, 2013. [PubMed: 24076603] [Full Text: https://doi.org/10.1038/ng.2776]
Schaller, F., Watrin, F., Sturny, R., Massacrier, A., Szepetowski, P., Muscatelli, F. A single postnatal injection of oxytocin rescues the lethal feeding behaviour in mouse newborns deficient for the imprinted Magel2 gene. Hum. Molec. Genet. 19: 4895-4905, 2010. [PubMed: 20876615] [Full Text: https://doi.org/10.1093/hmg/ddq424]
Soden, S. E., Saunders, C. J., Willig, L. K., Farrow, E. G., Smith, L. D., Petrikin, J. E., LePichon, J.-B., Miller, N. A., Thiffault, I., Dinwiddie, D. L., Twist, G., Noll, A., and 15 others. Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders. Sci. Transl. Med. 6: 265ra168, 2014. [PubMed: 25473036] [Full Text: https://doi.org/10.1126/scitranslmed.3010076]
Urreizti, R., Cueto-Gonzalez, A. M., Franco-Valls, H., Mort-Farre, S., Roca-Ayats, N., Ponomarenko, J., Cozzuto, L., Company, C., Bosio, M., Ossowski, S., Montfort, M., Hecht, J., Tizzano, E. F., Cormand, B., Vilageliu, L., Opitz, J. M., Neri, G., Grinberg, D., Balcells, S. A de novo nonsense mutation in MAGEL2 in a patient initially diagnosed as Opitz-C: similarities between Schaaf-Yang and Opitz-C syndromes. Sci. Rep. 7: 44138, 2017. Note: Electronic Article. [PubMed: 28281571] [Full Text: https://doi.org/10.1038/srep44138]