Zrhidri Abdelali, Amasdl Saadia, Lyahyai Jaber, Elouardi Hanane, Chkirate Bouchra, Raymond Laure, Egéa Grégory, Taoudi Mohamed, El Mouatassim Said, Sefiani Abdelaziz
Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Mohammed V University, Rabat, Morocco.
Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco.
Pediatr Rheumatol Online J. 2017 Sep 26;15(1):72. doi: 10.1186/s12969-017-0200-2.
Scleroderma is a multisystem disease, characterized by fibrosis of skin and internal organs, immune dysregulation, and vasculopathy. The etiology of the disease remains unknown, but it is likely multifactorial. However, the genetic basis for this condition is defined by multiple genes that have only modest effect on disease susceptibility.
Three Moroccan siblings, born from non-consanguineous Moroccan healthy parents were referred for genetic evaluation of familial scleroderma. Whole Exome Sequencing was performed in the proband and his parents, in addition to Sanger sequencing that was carried out to confirm the results obtained.
Mutation analysis showed two compound heterozygous mutations c.196C>T in exon 4 and c.635_636delTT in exon 9 of GNPTG gene. Sanger sequencing confirmed these mutations in the affected patient and demonstrated that their parents are heterozygous carriers.
Our findings expand the mutation spectrum of the GNPTG gene and extend the knowledge of the phenotype-genotype correlation of Mucolipidosis Type III gamma. This report also highlights the diagnostic utility of Next Generation Sequencing particularly when the clinical presentation did not point to specific genes.
硬皮病是一种多系统疾病，其特征为皮肤和内脏器官纤维化、免疫失调及血管病变。该病病因不明，但可能是多因素所致。然而，这种疾病的遗传基础由多个对疾病易感性仅有适度影响的基因所决定。
三名出生于非近亲摩洛哥健康父母的摩洛哥兄弟姐妹因家族性硬皮病接受基因评估。除了进行桑格测序以确认所得结果外，还对先证者及其父母进行了全外显子组测序。
突变分析显示GNPTG基因外显子4中的两个复合杂合突变c.196C>T和外显子9中的c.635_636delTT。桑格测序在患病患者中证实了这些突变，并表明其父母为杂合携带者。
我们的研究结果扩展了GNPTG基因的突变谱，并扩展了对III型γ-粘脂贮积症表型-基因型相关性的认识。本报告还强调了下一代测序的诊断效用，尤其是当临床表现未指向特定基因时。
