Meckel-Gruber综合征(MKS,OMIM#607361)是一种罕见的产前或围产期致命的常染色体隐性遗传性纤毛病,由至少12个已知基因的突变引起。它与其他可行的纤毛病变有临床和遗传重叠,特别是Joubert综合征和Joubert综合征相关疾病。MKS的特点是多囊性肾发育不良,中枢神经系统畸形(通常是枕骨脑膨出),肝导管板畸形,后轴多指。
我们在受MKS影响的胎儿中发现了TMEM67(MKS3)的纯合突变;然而,只有母亲是各自突变的携带者。用多态微卫星标记和单核苷酸多态性(SNP)阵列进行的基因分型揭示了整个8号染色体(upd(8)mat)的母本单亲二体(UPD),窝藏TMEM67.
这是首例报告的UPD作为MKS的原因。回顾了单亲二体(UPD)的可能潜在机制。即使罕见,对UPD的认识和在隐性突变的意外纯合性的情况下的全面检查对于准确的遗传咨询和复发风险评估至关重要.
Meckel-Gruber syndrome (MKS, OMIM #607361) is a rare pre- or perinatal lethal autosomal recessive ciliopathy caused by mutations in at least 12 known genes. It has a clinical and genetic overlap with other viable ciliopathies, especially Joubert syndrome and Joubert syndrome-related disorders. MKS is characterized by multicystic kidney dysplasia, central nervous system malformations (usually occipital encephalocele), ductal plate malformation of the liver, and postaxial polydactyly.
We identified a homozygous mutation in TMEM67 (MKS3) in a fetus affected by MKS; however, only the mother was a carrier of the respective mutation. Genotyping with polymorphic microsatellite markers and single nucleotide polymorphism (SNP) array revealed a maternal uniparental disomy (UPD) of the entire chromosome 8 (upd(8)mat), harboring TMEM67.
This is the first reported case of UPD as a cause of MKS. The possible underlying mechanisms for uniparental disomy (UPD) are reviewed. Even if rare, awareness of UPD and comprehensive work-up in the case of unexpected homozygosity for a recessive mutation is essential for accurate genetic counseling and assessment of the risk of recurrence.