Abstract：
BACKGROUND: Rearrangements of unstable DNA sequences may alter the structural integrity or the copy number of dose-sensitive genes, resulting in copy number variations. They may lead more frequently to deletions, in addition to duplications and/or inversions, which are the underlying pathogenic mechanism of a group of conditions known as genomic disorders (or also contiguous gene syndromes). Interstitial deletions of the short arm of chromosome 1 are rare, and only about 30 patients have been reported. Their clinical features are variable, in respect of the extent of the deleted region. They include global developmental delay, central nervous system (CNS) malformations, craniosynostosis, dysmorphic face, ocular defects, cleft palate, urinary tract anomalies and hand/foot abnormalities.
METHODS: Hereby, we report on an Italian female newborn with craniosynostosis, facial dysmorphisms including bilateral microphthalmia and coloboma, cleft palate, and a severe global developmental and growth delay, associated to a 1p31.3p22.2 deletion of 20.7 Mb. This was inherited from the healthy mother, who was carrier of a smaller (2.6 Mb) deletion included within the centromeric region (1p22.3p22.2) of the same rearrangement, in addition to a translocation between chromosomes 1p and 4q. The deleted region of the proband contains about ninety genes. We focus on the genotype-phenotype correlations.
CONCLUSIONS: The results of the present study further confirm that microdeletions at 1p31.3 constitute a contiguous gene syndrome. It is hard to establish whether the critical rearrangement of such syndrome may involve the centromeric band p22.3p22.2, or more likely do not, also in light of the genomic profile of the healthy mother of our patient. Neonatologists and pediatricians should take into consideration 1p31 microdeletion in cases of developmental and growth delay associated to craniosynostosis, peculiar facial dysmorphisms, cleft palate and hand/foot abnormalities. The present report provides new data about 1p31 microdeletion syndrome, in view of a better characterization of its genomic and phenotypic profile.
METHODS: Hereby, we report on an Italian female newborn with craniosynostosis, facial dysmorphisms including bilateral microphthalmia and coloboma, cleft palate, and a severe global developmental and growth delay, associated to a 1p31.3p22.2 deletion of 20.7 Mb. This was inherited from the healthy mother, who was carrier of a smaller (2.6 Mb) deletion included within the centromeric region (1p22.3p22.2) of the same rearrangement, in addition to a translocation between chromosomes 1p and 4q. The deleted region of the proband contains about ninety genes. We focus on the genotype-phenotype correlations.
CONCLUSIONS: The results of the present study further confirm that microdeletions at 1p31.3 constitute a contiguous gene syndrome. It is hard to establish whether the critical rearrangement of such syndrome may involve the centromeric band p22.3p22.2, or more likely do not, also in light of the genomic profile of the healthy mother of our patient. Neonatologists and pediatricians should take into consideration 1p31 microdeletion in cases of developmental and growth delay associated to craniosynostosis, peculiar facial dysmorphisms, cleft palate and hand/foot abnormalities. The present report provides new data about 1p31 microdeletion syndrome, in view of a better characterization of its genomic and phenotypic profile.
摘要：
背景：不稳定DNA序列的重排可能会改变剂量敏感基因的结构完整性或拷贝数，导致拷贝数变化。它们可能会导致更频繁的删除，除了复制和/或反转，这是一组称为基因组疾病（或连续基因综合征）的疾病的潜在致病机制。1号染色体短臂的间质缺失很少见，只有大约30名患者被报告。他们的临床特征是可变的，关于删除区域的范围。它们包括全球发育迟缓，中枢神经系统（CNS）畸形，颅骨融合症,异形面，眼部缺陷,腭裂,尿路异常和手/足异常。
方法：特此，我们报道了一名意大利女性新生儿颅骨融合症，面部畸形，包括双侧小眼症和结肠缺损，腭裂,以及严重的全球发展和增长延迟，与20.7Mb的1p31.3p22.2缺失相关。这是从健康的母亲那里遗传下来的，谁是在相同重排的着丝粒区域（1p22.3p22.2）内包含较小（2.6Mb）缺失的携带者，除了染色体1p和4q之间的易位。先证者的缺失区含有约90个基因。我们专注于基因型-表型相关性。
结论：本研究的结果进一步证实，1p31.3的微缺失构成了一个连续的基因综合征。很难确定这种综合征的关键重排是否可能涉及着丝粒带p22.3p22.2，或者更有可能不涉及，也根据我们病人健康母亲的基因组概况。新生儿科医师和儿科医生应在与颅骨融合相关的发育和生长延迟的情况下考虑1p31微缺失，特殊的面部畸形，腭裂和手/足异常。本报告提供了有关1p31微缺失综合征的新数据，鉴于其基因组和表型谱的更好表征。
方法：特此，我们报道了一名意大利女性新生儿颅骨融合症，面部畸形，包括双侧小眼症和结肠缺损，腭裂,以及严重的全球发展和增长延迟，与20.7Mb的1p31.3p22.2缺失相关。这是从健康的母亲那里遗传下来的，谁是在相同重排的着丝粒区域（1p22.3p22.2）内包含较小（2.6Mb）缺失的携带者，除了染色体1p和4q之间的易位。先证者的缺失区含有约90个基因。我们专注于基因型-表型相关性。
结论：本研究的结果进一步证实，1p31.3的微缺失构成了一个连续的基因综合征。很难确定这种综合征的关键重排是否可能涉及着丝粒带p22.3p22.2，或者更有可能不涉及，也根据我们病人健康母亲的基因组概况。新生儿科医师和儿科医生应在与颅骨融合相关的发育和生长延迟的情况下考虑1p31微缺失，特殊的面部畸形，腭裂和手/足异常。本报告提供了有关1p31微缺失综合征的新数据，鉴于其基因组和表型谱的更好表征。
