Supplementary Material for: Meckel–Gruber syndrome due to homozygous c.16del (p.Leu6SerfsTer15) variant in the TCTN1: first case from Türkiye

Introduction: Meckel–Gruber syndrome (MKS) is a clinically and genetically heterogeneous ciliopathy characterized by a triad of occipital encephalocele, polycystic kidneys, and postaxial polydactyly. Almost all of them are lethal in the prenatal or first postnatal periods. It is usually diagnosed clinically with a detailed prenatal ultrasound examination. Variants have been reported in at least 14 different genes.
Case Presentation: We report a male fetus with oligohydramnios, large kidneys with microcysts covering the entire abdomen, postaxial polydactyly of the hands, bilateral pes equinovarus, encephalocele, microphthalmia, short extremities, and a mass lesion under the diaphragm. Termination was recommended to the family due to severe findings. Fetal skin biopsy and parental peripheral blood samples were obtained to investigate the potential pathogenic variants associated with MKS via clinical exome sequencing and Sanger sequencing.
Results and Conclusion: The fetus was homozygous for the c.16del (p.Leu6SerfsTer15) variant in the TCTN1 (NM_001082538.3), and both parents were heterozygous for the variant. Genetic diagnosis is very important in terms of counseling for subsequent pregnancies. To our knowledge, this is the third Meckel Gruber case in the literature caused by the TCTN1, and a novel likely pathogenic variant was detected.

引言：梅克尔-格鲁伯综合征（Meckel–Gruber syndrome, MKS）是一种临床与遗传异质性纤毛病，以枕部脑膨出、多囊肾及轴后多指（趾）三联征为典型特征。该病几乎所有病例均于产前或产后早期致死，通常可通过详细的产前超声检查作出临床诊断。目前已在至少14种不同基因中报道了与其相关的致病变异。
病例报告：本文报道1例男性胎儿，临床表现为羊水过少、全腹布满微囊的增大肾脏、手部轴后多指（趾）、双侧马蹄内翻足、脑膨出、小眼球、肢体短小以及膈下占位性病变。鉴于患儿病情危重，向家属建议终止妊娠。采集胎儿皮肤活检样本与父母外周血样本，通过临床外显子组测序及桑格测序（Sanger sequencing），探究与MKS相关的潜在致病变异。
结果与结论：该胎儿携带TCTN1基因（NM_001082538.3）c.16del（p.Leu6SerfsTer15）变异的纯合突变，其父母均为该变异的杂合携带者。遗传诊断对于后续妊娠的遗传咨询具有重要价值。据我们所知，本例为文献报道的第三例由TCTN1变异导致的梅克尔-格鲁伯综合征病例，且检出了一种新型疑似致病变异。