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Background: Vici syndrome (VICIS) refers to a clinical spectrum of multiple organ systems characterized by corpus callosum agenesis, hypopigmentation, cataracts, cardiomyopathy and immunodeficiency. The aims of this study were to describe detailed clinical and molecular features of two Chinese female siblings and to review several previous findings. Methods: Targeted sequencing panel involving all known disease‐causing genes of monogenic disorders combined with Sanger sequencing validation were performed to identify the likely pathogenic sequence variants of the proband with VICIS. Results: The proband diagnosed as VICIS presented with neonatal pneumonia, myocardial damage, hypotonia, maxillofacial malformations, hearing impairment, failure to thrive and died 40 days after birth. Two novel missense variants in ectopic P‐granules autophagy protein 5 homologue (EPG5, NM_020964.3) were identified in this proband. The two likely pathogenic variants c.1609G > A (p.(E537K)) and c.5764C>G (p.(P1922A)) were assessed as damaging by bioinformatic analysis. As these variants were absent in 150 unrelated Chinese normal controls and inherited from asymptomatic parents in the co‐segregation analysis, the compound heterozygous EPG5 variants were responsible for the clinical features of this patient. Finally, she was genetically diagnosed with VICIS. Conclusions: To our knowledge, this is the first Chinese case of VICIS. Our report identified novel compound heterozygous EPG5 sequence variants in the proband with VICIS, highlighting the rarity and high mortality rate of VICIS and emphasizing on the importance of high‐throughput sequencing in confirmed diagnosis of monogenic diseases, which could further facilitate the development of genetic counselling and prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Background: The dysferlin gene or the DYSF gene encodes the Ca2+‐dependent phospholipid‐binding protein dysferlin, which belongs to the ferlin family and is associated with muscle membrane regeneration and repair. Variants in the DYSF gene are responsible for limb‐girdle muscular dystrophy type 2B (LGMD2B), also called limb‐girdle muscular dystrophy recessive 2 (LGMDR2), a rare subtype of muscular dystrophy involving progressive muscle weakness and atrophy. The present study aimed to identify the variants responsible for the clinical symptoms of a Chinese patient with limb girdle muscular dystrophies (LGMDs) and to explore the genotype–phenotype associations of LGMD2B. Methods: A series of clinical examinations, including blood tests, magnetic resonance imaging scans for the lower legs, electromyography and muscle biopsy, was performed on the proband diagnosed with muscular dystrophies. Whole exome sequencing was conducted to detect the causative variants, followed by Sanger sequencing to validate these variants. Results: We identified two compound heterozygous variants in the DYSF gene, c.1058 T>C, p.(Leu353Pro) in exon 12 and c.1461C>A/p.Cys487* in exon 16 in this proband, which were inherited from the father and mother, respectively. In silico analysis for these variants revealed deleterious results by PolyPhen‐2 (Polymorphism Phenotyping v2; http://genetics.bwh.harvard.edu/pph2), SIFT (Sorting Intolerant From Tolerant; https://sift.bii.a-star.edu.sg), PROVEAN (Protein Variation Effect Analyzer; http://provean.jcvi.org/seq%5fsubmit.php) and MutationTaster (http://www.mutationtaster.org). In addition, the two compound heterozygous variants in the proband were absent in 100 control individuals who had an identical ethnic origin and were from the same region, suggesting that these variants may be the pathogenic variants responsible for the LGMD2B phenotypes for this proband. Conclusions: The present study broadens our understanding of the mutational spectrum of the DYSF gene, which provides a deep insight into the pathogenesis of LGMDs and accelerates the development of a prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Background: Autosomal recessive congenital ichthyosis (ARCI) is a rare genetically heterogeneous cutaneous disease predominantly characterized by erythroderma, generalized abnormal scaling of the whole body and a collodion membrane at birth. Numerous causative genes have been demonstrated to be responsible for ARCI including PNPLA1 which can cause ARCI type 10. The objectives of this study are to describe clinical features of three ARCI patients from two Chinese unrelated families and to identify the underlying causative mutations. Methods: Genomic DNA was extracted from peripheral venous blood obtained from the two Chinese ARCI families in Shandong province. Subsequently, targeted regions sequencing (TRS) followed by Sanger sequencing was conducted to identify and validate the likely pathogenic mutations of the ARCI families. Results: Genetic analyses revealed four novel PNPLA1 variants that are predicted to be probably to lead to ARCI in three patients of two families. Patient 1 in one family was in compound heterozygous status for c.604delC/p.Arg202Glyfs*27 and c.820dupC/p.Arg274Profs*15, whereas c.738_742delinsCCCACAGATCCTGC/ p.Gly247_Tyr248delinsProGlnIleLeuHis, and c.816dupC/p.Arg274Profs*15 were found in patient 2 and 3 of the other family. In addition, these variants cosegregate in the two pedigrees and are all within highly conserved regions of the PNPLA1 protein, which indicate that the four mutations are likely pathogenic. Conclusion: Our findings not only broaden the mutational spectrum of PNPLA1, but also contribute to establishing genotype–phenotype correlations for different forms of ARCI. [ABSTRACT FROM AUTHOR]