A novel large deletion mutation of FERMT1 gene in a Chinese patient with Kindler syndrome

Abstract

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.

A novel frameshift mutation in the <em>FERMT1</em> gene in a Chinese patient with Kindler syndrome

“…To date, c.1885_1901del (p.Val629fs) is the 5th reported mutation in Chinese patients with KS, with the other four mutations including three deletion mutations: c.994_995delCA (17), a 17252-bp deletion mutation (18) and g.63601_66617del (14), and one missense mutation, c.1343T>A (p.Met448Lys) (19). c.994_995delCA was the only mutation that was recurrent and was also reported in the Iranian population (20).…”

A report and review of the recurrent c.811C>T variant and mutation spectrum of Kindler syndrome in East Asians: a diagnostic odyssey of 2 weeks versus 49 years

“…Homozygous frameshift mutations, including c.220delC in exon 3, c.994_995delCA in exon 8, and c.1885_1901del in exon 15, were reported in three Chinese patients, all of which were predicted to cause a premature stop codon [23][24][25] . Ohashi et al observed homozygous nonsense variant c.1761T>A in a Japanese patient and Li et al reported two compound heterozygous nonsense mutations (c.193C>T, c.277C>T) in a Chinese patient [23,26] . Large deletion caused by Matrix Attachment Region elements mediated homologous recombination or Alu-mediated homologous recombination has been reported in two Chinese patients born to consanguineous parents, one of which is a 3017-bp deletion mutation spanning exons 7-9 (g.63601_66617del) and the other one is a 17kb homozygous deletion spanning the introns 1-6, both are presumed to cause nonsense-mediated mRNA decay [27,28] .…”

Clinical practice guidelines: Oral health care for children and adults living with epidermolysis bullosa

“…[186][187][188] Multiple single-patient reports also highlight gingival health as a major concern, 132,133 including a 14-year-old patient who lost all of her teeth due to severe periodontitis. 161 Most of the descriptions of periodontal disease in patients with KEB have been published by medical teams; therefore, the authors use more general terms such as: halitosis, 164,177 gingivitis, 156,160,163,164,[180][181][182][183]189,190,191 severe gingivitis, 164,168,192,193 erosive stomatitis, 194 desquamative gingivitis, 155,160,165 easy bleeding, 155,157,164,167,[180][181][182]195,196 gingival hypertrophy, 162,178,197 periodontitis, 135,[157][158][159]162,164,178,180,184,…”

“…Multiple single‐patient reports also highlight gingival health as a major concern, 132,133 including a 14‐year‐old patient who lost all of her teeth due to severe periodontitis 161 . Most of the descriptions of periodontal disease in patients with KEB have been published by medical teams; therefore, the authors use more general terms such as: halitosis, 164,177 gingivitis, 156,160,163,164,180–183,189,190,191 severe gingivitis, 164,168,192,193 erosive stomatitis, 194 desquamative gingivitis, 155,160,165 easy bleeding, 155,157,164,167,180–182,195,196 gingival hypertrophy, 162,178,197 periodontitis, 135,157–159,162,164, 178,180,184,190,198–201 severe periodontitis, 161,165,173,192,195,196 severe periodontal bone loss, 155 “missing teeth,” “loss of teeth,” or “poor preservation of teeth,” 135,158,160,161, 167,168,173,184,190,195,196,200,202 and gingiva with pseudomembranous necrotic and bleeding areas 173 . Interestingly, and in contrast to RDEB where poor hygiene is widely reported, only few reports describe poor dental hygiene; even though the severity of periodontal disease in KEB is more complex (Image 2.22).…”