已知CCN6基因中的双等位基因突变会导致罕见的遗传性疾病-进行性假性类风湿发育不良(PPD)。PPD的特点是指间关节明显的关节畸形,刚度,步态紊乱,异常姿势,没有炎症,导致严重的发病率。来自印度的最大的PPD病例系列表明c.233G>A和c.1010G>A是CCN6基因中最常见的突变,尽管这些变体在印度的内婚社区中的分布尚未进行。我们在这里报告了来自古吉拉特邦Patni社区的三个独立家庭的三例PPD,一个以实行内婚制而闻名的社区。这三例都有身材矮小,步态紊乱,脊柱侧弯,指间关节畸形。在第一个病例中通过全外显子组测序分析显示存在一个先前已知的,纯合子,错义变体c.298T>A(p.Cys100Ser)在所有情况下都在CCN6基因的外显子3中。由于所有三个家庭都属于同一个社区,通过Sanger测序在其余两个病例中对前面提到的变体进行的分析显示,这两个病例都是纯合突变基因型。不受影响的家庭成员,即,父母和兄弟姐妹,是所述变体的杂合携带者或野生型。本病例系列是第一份报告,涉及来自印度同一社区的不相关家庭的多个受PPD影响的个体的复发性变异。
Biallelic mutations in the
CCN6 gene are known to cause a rare genetic disorder-progressive pseudorheumatoid dysplasia (PPD). PPD is characterized by distinct joint deformities of interphalangeal joints, stiffness, gait disturbance, abnormal posture, and absence of inflammation, resulting in significant morbidity. The largest
case series of PPD from India suggests c.233G>A and c.1010G>A to be the most common mutations in the
CCN6 gene, although the distribution of these variants among endogamous communities in India has not been carried out. We here report three cases of PPD from three independent families belonging to the Patni community of Gujarat, a community known to practice endogamy. All three cases had short stature, gait disturbance, scoliosis, and interphalangeal joint deformities. Analysis by whole-exome sequencing in the first
case showed the presence of a previously known, homozygous, missense variant c.298T>A (p.Cys100Ser) in exon 3 of the
CCN6 gene in all cases. Due to all three families belonging to the same community, analysis by Sanger sequencing in the remaining two cases for the variant mentioned earlier showed both cases to be of homozygous mutant genotype. Unaffected family members, i.e., parents and siblings, were either heterozygous carriers or wildtype for the said variant. The present case series is the first report of a recurrent variant occurring across multiple PPD-affected individuals from unrelated families belonging to the same community from India.