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Objective:To study the clinical features, treatment, and prognostic features of Kaufman Oculocerebrofacial syndrome.Methods:The clinical characteristics of a newborn with Kaufman Oculocerebrofacial syndrome admitted to the neonatal unit of Guiyang Maternal and Child Health Care Hospital was reported. Using "Kaufman Oculocerebrofacial syndrome", "Blepharophimosis-ptosis-intellectual disability syndrome" and "UBE3B gene" as keywords, databases including CNKI, VIP database, Wanfang database, Chinese medical journals full-text database, PubMed, Web of Science database and Embase database were searched from the date of establishment to June 2022. The clinical characteristics, treatment and prognosis of Kaufman Oculocerebrofacial syndrome from published literature were summarized.Results:The proband was a boy presenting with small lid fissure, wide eye spacing and feeding difficulties. Whole exome sequencing revealed compound heterozygous mutation in the UBE3B gene, c.1445_1448dupTCAC inherited from his father and c.1703dupA inherited from his mother, both variants had not been reported in the domestic and foreign literature thus far. A total of 34 newborn cases were summarized from 11 case reports, including this report. The main clinical manifestations were developmental delay (35/35), peculiar facial features (35/35), narrow eye slits (35/35), feeding difficulties (33/35), ear abnormalities (33/35), hypotonia (32/35), mouth abnormalities (31/35), breathing difficulties (26/35), small jaws (25/35) and low birth weight (16/35).There is no effective treatment available, and a total of 4 cases followed up to over 16 years old have been reported, all of which have severe mental retardation, language deficiency, along with other serious neurological diseases.Conclusions:when children exhibit symptoms such as narrow eye fissures, feeding difficulties, hypotonia, developmental delays, and peculiar facial features in the neonatal period, whole exome sequence can be used to aid diagnosis and evaluate for Kaufman Oculocerebrofacial syndrome. Families with children of Kaufman Oculocerebrofacial syndrome may undergo prenatal diagnosis based on genetic findings.
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Genetic patterns of inter-population variation are a result of different demographic and adaptive histories, which gradually shape the frequency distribution of the variants. However, the study of clinically relevant mutations has a Eurocentric bias. The Romani, the largest transnational minority ethnic group in Europe, originated in South Asia and received extensive gene flow from West Eurasia. Most medical genetic studies have only explored founder mutations related to Mendelian disorders in this population. Here we analyze exome sequences and genome-wide array data of 89 healthy Spanish Roma individuals to study complex traits and disease. We apply a different framework and focus on variants with both increased and decreased allele frequencies, taking into account their local ancestry. We report several OMIM traits enriched for genes with deleterious variants showing increased frequencies in Roma or in non-Roma (e.g., obesity is enriched in Roma, with an associated variant linked to South Asian ancestry; while non-insulin dependent diabetes is enriched in non-Roma Europeans). In addition, previously reported pathogenic variants also show differences among populations, where some variants segregating at low frequency in non-Roma are virtually absent in the Roma. Lastly, we describe frequency changes in drug-response variation, where many of the variants increased in Roma are clinically associated with metabolic and cardiovascular-related drugs. These results suggest that clinically relevant variation in Roma cannot only be characterized in terms of founder mutations. Instead, we observe frequency differences compared to non-Roma: some variants are absent, while other have drifted to higher frequencies. As a result of the admixture events, these clinically damaging variants can be traced back to both European and South Asian-related ancestries. This can be attributed to a different prevalence of some genetic disorders or to the fact that genetic susceptibility variants are mostly studied in populations of European descent, and can differ in individuals with different ancestries.
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Inflammatory bowel disease (IBD) is a group of chronic disorders that cause relapsing inflammation in the gastrointestinal tract and comprise three major subgroups of Crohn's disease (CD), ulcerative colitis (UC), and IBD-unclassified (IBDU). Recent advances in genomic technologies have furthered our understanding of IBD pathogenesis. It includes differentiation rare monogenic disorders exhibiting IBD and IBD-like inflammation (monogenic IBD) from patients with the common polygenic form of IBD. Several novel genes responsible for monogenic IBD have been elucidated, and the number of reports has increased due to advancements in molecular functional analysis. Identification of these pathogenic genetic mutations has helped in elucidating the details of the immune response associated with gastrointestinal inflammation and in providing individualized treatments for patients with severe IBD that is often unresponsive to conventional therapy. The majority of monogenic IBD studies have focused on young children diagnosed <6 years of age (very early-onset IBD); however, a recent study revealed high prevalence of monogenic IBD in older children aged >6 years of age as well. Meanwhile, although patients with monogenic IBD generally show co-morbidities and/or extraintestinal manifestation at the time of diagnosis, cases of IBD developing as the initial symptom with unremarkable prodromal symptoms have been reported. It is crucial that the physicians properly match genetic analytical data with clinical diagnosis and/or differential diagnosis. In this review, we summarize the essential clues that may physicians make a correct diagnosis of monogenic disease, including classification, prevalence and clinical phenotype based on available literatures.
