Angelman syndrome (AS) is a neurobehavioral disorder caused by lack of function of the maternal copy of the ubiquitin-protein ligase E3A (UBE3A) gene. In our study, 49 unrelated patients with classic AS phenotypes were confirmed by methylation-specific PCR (MS-PCR) analysis, short tandem repeat linkage analysis, and mutation screening of the UBE3A gene. Among the Chinese AS patients, 83.7% (41/49) had deletions on maternal chromosome 15q11.2-13. Paternal uniparental disomy, imprinting defects, and UBE3A gene mutations each accounted for 4.1% (2/49). Two AS patients were confirmed by MS-PCR analysis, but the pathogenic mechanism was unknown because their parents' samples were unavailable. Of the two described UBE3A gene mutations, that is, p.Pro400His (c.1199C>A) and p.Asp563Gly (c.1688A>G), the latter has not been reported previously. Mutation transmission analysis showed that the p.Pro400His and p.Asp563Gly mutations originated from asymptomatic mothers. The patients with the maternal deletion showed AS clinical manifestations that were consistent with other studies. However, the incidence of microcephaly (36.7%, 11/30) was lower than that in the Caucasian population (approximately 80%), but similar to that of the Japanese population (34.5%). Our study demonstrated that the occurrence of microcephaly in AS may vary among different populations.

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Abstract:Kindler syndrome (KS; OMIM 173650) is a rare autosomal recessive skin disorder, which results in symptoms including blistering, epidermal atrophy, increased risk of cancer, and poor wound healing. The majority of mutations of the disease-determining gene (FERMT1 gene) are single nucleotide substitutions, including missense mutations, nonsense mutations, etc. Large deletion mutations are seldom reported. To determine the mutation in the FERMT1 gene associated with a 7-year-old Chinese patient who presented clinical manifestation of KS, we performed direct sequencing of all the exons of FERMT1 gene. For the exons 2-6 without amplicons, we analyzed the copy numbers using quantitative real-time polymerase chain reaction (qRT-PCR) with specific primers. The deletion breakpoints were sublocalized and the range of deletion was confirmed by PCR and direct sequencing. In this study, we identified a new 17-kb deletion mutation spanning the introns 1-6 of FERMT1 gene in a Chinese patient with severe KS phenotypes. Her parents were carriers of the same mutation. Our study reported a newly identified large deletion mutation of FERMT1 gene involved in KS, which further enriched the mutation spectrum of the FERMT1 gene.

Hyaline fibromatosis syndrome (HFS; MIM 228600) is a rare autosomal recessive disorder characterized by the abnormal growth of hyalinized fibrous tissue at subcutaneous regions on the scalp, ears and neck. The disease is caused by either a homozygous or compound heterozygous mutation of the anthrax toxin receptor 2 (ANTXR2) gene. The present study describes a patient with HFS confirmed by clinical examination as well as histopathological and genetic analyses. Numerous painless and variable‑sized subcutaneous nodules were observed on the scalp, ear, trunk and four extremities of the patient. With increasing age, the number and size of the nodules gradually increased in the patient. The patient additionally presented with severe gingival thickening and developed pearly papules on the ears, back and penis foreskin. Biopsies of ear nodules revealed that the tumor was located in the dermis, and no marked alterations were observed in the epidermis compared with healthy patients. Spindle‑shaped or round tumor cells were revealed to be immersed in the eosinophilic hyaline ground substance. Furthermore, a skeletal X‑ray of the patient revealed multiple low‑density imaging on the right distal humerus. Compound heterozygous mutations in the ANTXR2 gene were identified in the patient: c.470_472del in exon 5 and c.1073 delC in exon 13. c.470_472del were revealed to be inherited from his mother and father, respectively. These two mutations, c.470_472del and c.1073 delC, to the best of our knowledge, have not previously been identified. Identification of the mutations in ANTXR2 may make prenatal diagnosis of HFS possible during future pregnancies.

Abstract:Crigler-Najjar syndrome type I (CN-I) is the most severe type of hereditary unconjugated hyperbilirubinemia. It is caused by homozygous or compound heterozygous mutations of the UDP-glycuronosyltransferase gene (UGT1A1) on chromosome 2q37. Two patients clinically diagnosed with CN-I were examined in this paper. We sequenced five exons and their flanking sequences, specifically the promoter region of