Ullah Ikram, Aamir Muhammad, Ilyas Muhammad, Ahmed Akmal, Jelani Musharraf, Ullah Wahid, Abbas Muhammad, Ishfaq Muhammad, Ali Fawad, Yip Janice, Efthymiou Stephanie, Ahmed Habib, Houlden Henry
Centre for Omic Sciences, Islamia College Peshawar, Peshawar, Pakistan.
Centre for Human Genetics, Hazara University Mansehra, Mansehra, Pakistan.
Congenit Anom (Kyoto). 2021 Sep;61(5):177-182. doi: 10.1111/cga.12436. Epub 2021 Jul 13.
The Ehlers-Danlos syndrome (EDS) is a group of heritable connective tissue disorders. Common features of EDS include skin hyperextensibility, articular hypermobility, and tissue fragility. It is classified into 13 subtypes, caused by variations of more than 19 different genes. Among these two subtypes, EDS musculocontractural type 1 (EDSMC1/mcEDS-CHST14; MIM# 601776) is caused by biallelic mutations in the CHST14 gene (MIM# 608429) on chromosome 15q14 and EDS musculocontractural type 2 (EDSMC2/mcEDS-DSE;MIM#615539) is caused by a mutation in DSE (MIM# 605942) on chromosome 6q22. In this study, clinical and molecular diagnoses have been performed for a consanguineous Pakistani (Pakhtun) family with five affected siblings, presenting mcEDS-DSE phenotype. Whole-exome sequencing analysis identified a novel homozygous DSE variant (NM_001080976.1; c.2813T>A, p.Val938Asp) in the proband. Sanger sequencing in all available affected members and their obligate carriers confirmed autosomal recessive segregation of the diseased allele. To the best of our knowledge, this variant identified is novel and expands the DSE pathogenicity leading to EDS, musculocontractural type 2. The result obtained has the potential to help in early diagnosis, genetic counseling, and possible therapeutic inventions.
埃勒斯-当洛综合征（EDS）是一组遗传性结缔组织疾病。EDS的常见特征包括皮肤过度伸展、关节活动过度和组织脆弱性。它被分为13个亚型，由19种以上不同基因的变异引起。在这两个亚型中，1型肌肉挛缩型EDS（EDSMC1/mcEDS-CHST14；MIM#601776）由15号染色体q14上CHST14基因（MIM#608429）的双等位基因突变引起，2型肌肉挛缩型EDS（EDSMC2/mcEDS-DSE；MIM#615539）由6号染色体q22上DSE（MIM#605942）的突变引起。在本研究中，对一个有五个患病兄弟姐妹、表现出mcEDS-DSE表型的巴基斯坦近亲（普什图族）家庭进行了临床和分子诊断。全外显子测序分析在先证者中鉴定出一种新的纯合DSE变异（NM_001080976.1；c.2813T>A，p.Val938Asp）。对所有可用的患病成员及其必然携带者进行的桑格测序证实了患病等位基因的常染色体隐性遗传。据我们所知，鉴定出的这种变异是新的，扩展了导致2型肌肉挛缩型EDS的DSE致病性。所获得的结果有可能有助于早期诊断、遗传咨询和可能的治疗干预。
