European Journal of Medical Genetics ( IF 1.9 ) Pub Date : 2020-05-26 , DOI: 10.1016/j.ejmg.2020.103958 Samina Yasin 1 , Saima Mustafa 2 , Arzoo Ayesha 2 , Muhammad Latif 3 , Mubashir Hassan 4 , Muhammad Faisal 5 , Outi Makitie 6 , Furhan Iqbal 2 , Sadaf Naz 1
Spondylo-epimetaphyseal dysplasia Matrilin 3 type (SEMD) is a rare autosomal recessive skeletal dysplasia characterized by short stature, abnormalities in the vertebral bodies and long bones, especially the lower limbs. We enrolled a consanguineous family from Pakistan in which multiple siblings suffered from severe skeletal dysplasia. The six affected subjects ranged in heights from 100 to 136 cm (~-6 standard deviation). Lower limb abnormalities with variable varus and valgus deformities and joint dysplasia were predominant features of the clinical presentation. Whole exome sequencing (WES) followed by Sanger sequencing identified a missense variant, c.542G > A, p.(Arg181Gln) in MATN3 as the genetic cause of the disorder. The variant was homozygous in all affected individuals while the obligate carriers had normal heights with no skeletal symptoms, consistent with a recessive pattern of inheritance. Multiple sequence alignment revealed that MATN3 domain affected by the variant is highly conserved in orthologous proteins. The c.542G > A, p.(Arg181Gln) variant is only the fourth variant in MATN3 causing an autosomal recessive disorder and thus expands the genotypic spectrum.
中文翻译:
MATN3中的一个新的纯合错义变体导致近亲家庭中的脊椎-肺ime突发育异常的基质胶3型。
脊椎-肺ime突发育不良基质素3型(SEMD)是一种罕见的常染色体隐性骨骼发育异常,其特征是身材矮小,椎体和长骨异常,尤其是下肢。我们从巴基斯坦招募了一个近亲家庭,其中多个兄弟姐妹患有严重的骨骼发育不良。六个受影响的对象的身高范围从100到136 cm(〜-6标准偏差)。下肢畸形伴内翻,外翻畸形和关节发育不良是临床表现的主要特征。整个外显子测序(WES),随后识别的错义变异体,c.542G> A,对Sanger测序。(Arg181Gln)在MATN3作为疾病的遗传原因。在所有受影响的个体中,该变异体是纯合的,而专性携带者的身高正常,没有骨骼症状,与遗传的隐性模式一致。多个序列比对揭示该变体影响的MATN3结构域在直系同源蛋白中高度保守。的c.542G> A,第(Arg181Gln)变体仅在第四变型MATN3引起的常染色体隐性疾病,从而扩大了基因型谱。