KBG syndrome in two patients from Egypt

Sayed, Inas S. M.; Abdel‐Hamid, Mohamed S.; Abdel-Salam, Ghada M H

doi:10.1002/ajmg.a.61552

Cited by 8 publications

(4 citation statements)

References 10 publications

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“…The primary finding of this study was the identification of a novel duplication locus at 16q24.3 (1.65 Mb), which was found in 19 RPL cases but in none of the SA cases. Deletions in 16q24.2 have been observed frequently in patients with KBG syndrome [33,34], autism spectrum disorder, intellectual disability and congenital renal malformation [30]. Moreover, 16q24.3 alterations aggravate the clinical outcomes of head and neck squamous cell carcinoma [35].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Copy-Number Variations and Possible Candidate Genes in Recurrent Pregnancy Losses

Sheng

Hou

et al. 2021

Genes

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It is well established that embryonic chromosomal abnormalities (both in the number of chromosomes and the structure) account for 50% of early pregnancy losses. However, little is known regarding the potential differences in the incidence and distribution of chromosomal abnormalities between patients with sporadic abortion (SA) and recurrent pregnancy loss (RPL), let alone the role of submicroscopic copy-number variations (CNVs) in these cases. The aim of the present study was to systematically evaluate the role of embryonic chromosomal abnormalities and CNVs in the etiology of RPL compared with SA. Over a 3-year period, 1556 fresh products of conception (POCs) from miscarriage specimens were investigated using single nucleotide polymorphism array (SNP-array) and CNV sequencing (CNV-seq) in this study, along with further functional enrichment analysis. Chromosomal abnormalities were identified in 57.52% (895/1556) of all cases. Comparisons of the incidence and distributions of chromosomal abnormalities within the SA group and RPL group and within the different age groups were performed. Moreover, 346 CNVs in 173 cases were identified, including 272 duplications, 2 deletions and 72 duplications along with deletions. Duplications in 16q24.3 and 16p13.3 were significantly more frequent in RPL cases, and thereby considered to be associated with RPL. There were 213 genes and 131 signaling pathways identified as potential RPL candidate genes and signaling pathways, respectively, which were centered primarily on six functional categories. The results of the present study may improve our understanding of the etiologies of RPL and assist in the establishment of a population-based diagnostic panel of genetic markers for screening RPL amongst Chinese women.

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Section: Discussionmentioning

confidence: 99%

Characterization of Copy-Number Variations and Possible Candidate Genes in Recurrent Pregnancy Losses

Sheng

Hou

et al. 2021

Genes

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“…The flow chart of the selected patients is shown in Figure 2 A. Only the KBGS patients with ANKRD11 gene variation were included ( n = 253) [ 2 , 5 , 8 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. The types of variations included frameshift variation ( n = 158), nonsense variation ( n = 61), copy number variation ( n = 13), missense variation ( n = 13), splice site variation ( n = 6), and deletion variation ( n = 2).…”

Section: Resultsmentioning

confidence: 99%

Genetic and Phenotypic Spectrum of KBG Syndrome: A Report of 13 New Chinese Cases and a Review of the Literature

Gao

Zhao

Cao

et al. 2022

JPM

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KBG syndrome (KBGS) is a rare autosomal dominant inherited disease that involves multiple systems and is associated with variations in the ankyrin repeat domain 11 (ANKRD11) gene. We report the clinical and genetic data for 13 Chinese KBGS patients diagnosed by genetic testing and retrospectively analyse the genotypes and phenotypes of previously reported KBGS patients. The 13 patients in this study had heterozygous variations in the ANKRD11 gene, including seven frameshift variations, three nonsense variations, and three missense variations. They carried 11 variation sites, of which eight were previously unreported. The clinical phenotype analysis of these 13 patients and 240 previously reported patients showed that the occurrence rates of craniofacial anomalies, dental anomalies, global developmental delays, intellectual disability/learning difficulties, limb anomalies, and behavioural anomalies were >70%. The occurrence rates of short stature, delayed bone age, and spinal vertebral body anomalies were >50%. The frequency of global developmental delays and intellectual disability/learning difficulties in patients with truncated ANKRD11 gene variation was higher than that in patients with missense variation in the ANKRD11 gene (p < 0.05). Collectively, this study reported the genotypic and phenotypic characteristics of the largest sample of KBGS patients from China and discovered eight new ANKRD11 gene variations, which enriched the variation spectrum of the ANKRD11 gene. Variation in the ANKRD11 gene mainly caused craniofacial anomalies, growth and developmental anomalies, skeletal system anomalies, and nervous system anomalies. Truncated variation in the ANKRD11 gene is more likely to lead to global growth retardation and intellectual disability/learning difficulties than missense variation in ANKRD11.

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“…The final number of patients included was 273 from 40 studies (online supplemental material). 7–10 13–48…”

Section: Resultsmentioning

confidence: 99%

Clinical description, molecular delineation and genotype–phenotype correlation in 340 patients with KBG syndrome: addition of 67 new patients

et al. 2022

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BackgroundKBG syndrome is a highly variable neurodevelopmental disorder and clinical diagnostic criteria have changed as new patients have been reported. Both loss-of-function sequence variants and large deletions (copy number variations, CNVs) involvingANKRD11cause KBG syndrome, but no genotype–phenotype correlation has been reported.Methods67 patients with KBG syndrome were assessed using a custom phenotypical questionnaire. Manifestations present in >50% of the patients and a ‘phenotypical score’ were used to perform a genotype–phenotype correlation in 340 patients from our cohort and the literature.ResultsNeurodevelopmental delay, macrodontia, triangular face, characteristic ears, nose and eyebrows were the most prevalentf (eatures. 82.8% of the patients had at least one of seven main comorbidities: hearing loss and/or otitis media, visual problems, cryptorchidism, cardiopathy, feeding difficulties and/or seizures. Associations found included a higher phenotypical score in patients with sequence variants compared with CNVs and a higher frequency of triangular face (71.1% vs 42.5% in CNVs). Short stature was more frequent in patients with exon 9 variants (62.5% inside vs 27.8% outside exon 9), and the prevalence of intellectual disability/attention deficit hyperactivity disorder/autism spectrum disorder was lower in patients with the c.1903_1907del variant (70.4% vs 89.4% other variants). Presence of macrodontia and comorbidities were associated with larger deletion sizes and hand anomalies with smaller deletions.ConclusionWe present a detailed phenotypical description of KBG syndrome in the largest series reported to date of 67 patients, provide evidence of a genotype–phenotype correlation between some KBG features and specificANKRD11variants in 340 patients, and propose updated clinical diagnostic criteria based on our findings.

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KBG syndrome in two patients from Egypt

Abstract: KBG syndrome is an intellectual disability (ID) associated with multiple congenital

Cited by 8 publications

References 10 publications

Characterization of Copy-Number Variations and Possible Candidate Genes in Recurrent Pregnancy Losses

Characterization of Copy-Number Variations and Possible Candidate Genes in Recurrent Pregnancy Losses

Genetic and Phenotypic Spectrum of KBG Syndrome: A Report of 13 New Chinese Cases and a Review of the Literature

Clinical description, molecular delineation and genotype–phenotype correlation in 340 patients with KBG syndrome: addition of 67 new patients

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