Achondrogenesis type 1A: clinical, histologic, molecular, and prenatal ultrasound diagnosis

Abstract

Sara Vanegas,1 Luz Fernanda Sua,2 Jaime López-Tenorio,3 Diana Ramírez-Montaño,1 Harry Pachajoa1,4 1Department of Basic Medical Sciences, Center for Research on Congenital Anomalies and Rare Diseases (CIACER), Universidad Icesi, Cali, Colombia; 2Department of Pathology and Laboratory Medicine, Fundación Valle del Lili, Cali, Colombia; 3Department of Obstetrics and Perinatology, Fundación Valle del Lili, Cali, Colombia; 4Department of Pediatric Medical Genetics, Fundación Valle del Lili, Cali, Colombia Background: Achondrogenesis type IA (ACG1A) is a rare, lethal autosomal recessive chondrodysplasia affecting endochondral bone ossification and differentiation, causing intrauterine growth restriction, narrow thorax, and short limbs. Mutations in TRIP11, which encodes Golgi microtubule-binding protein 210 in the Golgi apparatus, alter protein transport in tissues. Case presentation: A 28-week gestation male fetus was diagnosed with ACG1A by clinical, radiological, histologic, and molecular findings. Results: Whole exome sequencing was performed on fetal DNA and parental blood. Two fetal heterozygous novel variants of TRIP11, c.2304_2307delTCAA (p.Asn768Lysfs*7) and c.2128_2129delAT (p.lle710Cysfs*19), were inherited from the mother and father, respectively. Both variants created a reading frameshift leading to a premature stop codon and loss of protein function. Conclusion: To our knowledge, this is the first Latin American report with clinical, radiographic, and molecular diagnosis of ACG1A. Clinical and molecular diagnosis in utero is essential for genotype–phenotype correlation and is useful for providing better genetic counseling. Keywords: achondrogenesis type IA, endochondral bone, TRIP11, GMAP-210

Keywords

• Achondrogenesis type IA
• endochondral bone
• TRIP11
• GMAP-210