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American Journal of Medical Genetics Part AVolume 152A, Issue 6 p. fm x-fm x the AJMG SEQUENCEFree Access In this issue First published: 20 May 2010 https://doi.org/10.1002/ajmg.a.33536AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat GENE FOR CPN IDENTIFIED In a letter to the editor, Tanaka et al. (p. 1347) confirm the identification of the gene responsible for Clericuzio-type poikiloderma with neutropenia (CPN). CPN shares clinical anomalies with Rothmund-Thomson syndrome (RTS), so the discovery will help distinguish the 2 disorders, the researchers write. They pinpointed the culprit C16orf57 gene in their investigation of the molecular basis of CPN in a consanguineous 6-member Moroccan family [Mostefai et al. 2008]. The researchers genotyped the entire family including 3 unaffected parents, 3 affected offspring, and 1 unaffected offspring. Identification of the gene responsible for CPN will help physicians better anticipate myeloid anomalies and susceptibility to infections, researchers write. Nevertheless, the precise biological functions of C16orf57 remain largely unknown. Further assessment of C16orf57's function may help improve understanding of bone marrow and skin homeostasis and offer new insight into the pathophysiology of myeloid dysfunction, oxidative defects, and the cutaneous features of poikiloderma and photosensitivity, the researchers conclude. CLINICAL EFFECTS OF MUTATIONS IN BECKWITH-WIEDEMANN SYNDROME DESCRIBED Beckwith-Wiedemann syndrome (BWS) patients with CDKN1C mutations have a different pattern of clinical malformations than BWS patients with other molecular defects, write Romanelli et al. (p. 1390)2A. Figure 2AOpen in figure viewerPowerPoint Ribbon-plot representation of 3D model for CDKN1C / cyclin A-CDK2 complex interaction. BWS is an overgrowth syndrome characterized by macroglossia, macrosomia, and abdominal wall defects. The cause of the multigenic disorder is usually alterations in growth regulatory genes, but 5–10% of BWS patients have mutations in CDKN1C, a cyclin-dependent kinase inhibitor of G1 cyclin complexes that functions as a negative regulator of cellular growth and proliferation. To search for new mutations and to define genotype-phenotype correlations, the researchers analyzed 72 patients for CDKN1C defects, including 50 with BWS, 17 with isolated hemihyperplasia, 3 with omphalocele, and 3 with macroglossia. They identified 8 patients with BWS and CDKN1C mutations, including 7 novel mutations in CDKN1C. Their work brings the number of known mutations in the gene to 25. BWS patients with CDKN1C mutations may sometimes exhibit a different, heterogeneous pattern of clinical malformations than those with epigenetic/chromosomal abnormalities, the findings suggest. These anomalies include polydactyly, extra nipple, genital anomalies, and cleft palate. Identifying those clinical characteristics may be useful to focusing molecular analysis in BWS patients, researchers note. PRENATAL EXPOSURES A FACTOR IN SYNDROMIC METOPIC SYNOSTOSIS Prenatal exposures appear to contribute significantly to the syndromic form of metopic synostosis (MS), according to Kini et al. (p. 1383). To determine cause of MS, which accounts for approximately 10–15% of all craniosynostosis and is etiologically heterogeneous, the researchers reviewed case notes from 110 children diagnosed in a British craniofacial unit between 1991 and 20083. Figure 3Open in figure viewerPowerPoint Facial phenotype of children with chromosomal abnormalities and MS. Approximately two-thirds of all MS cases were nonsyndromic, the researchers found. They identified a link between exposure to the antiepileptic drug sodium valporate in doses of 1,000 mg or more per day and nonsyndromic MS, suggesting a preventable cause. Maternal diabetes, which has not been linked to MS previously, was seen in 5.5% of cases, suggesting maternal diabetes may also contribute to the etiology of MS. Chromosomal abnormalities were the second most common cause of syndromic MS. Deletions of chromosomes 9p23 and 11q24 have been previously associated with MS, while this study shows a possible susceptibility locus at 15q25. Studies of more MS cases are needed to confirm this finding. A significant proportion of children with MS had an additional structural abnormality but a normal karyotype. Array comparative genomic hybridization is indicated in such individuals, the researchers suggest. They also recommend neurodevelopmental surveillance in children with MS, because their review revealed developmental delay—particularly speech problems—in cases of both syndromic and nonsyndromic MS. Reference Mostefai R, Morice-Picard F, Boralevi F, Sautarel M, Lacombe D, Stasia MJ, McGrath J, Taïeb A. 2008. Poikiloderma with neutropenia, Clericuzio type, in a family from Morocco. Am J Med Genet Part A 146A: 2762– 2769. Volume152A, Issue6June 2010Pages fm x-fm x FiguresReferencesRelatedInformation