Sabbagh Quentin, Tharreau Mylène, Cenni Camille, Sanchez Elodie, Ruiz-Pallares Nathalie, Alkar Fanny, Amouroux Cyril, David Stéphanie, Prodhomme Olivier, Leboucq Nicolas, Meunier Isabelle, Bessis Didier, Theron Alexandre, Barat-Houari Mouna, Willems Marjolaine
Montpellier University, Service de Génétique Clinique, Centre de Compétence Maladies Osseuses Constitutionnelles, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
Montpellier University, Department of Molecular Genetics and Cytogenomics, Rare and Autoinflammatory Diseases Unit, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
Eur J Med Genet. 2023 May;66(5):104733. doi: 10.1016/j.ejmg.2023.104733. Epub 2023 Feb 25.
Autosomal recessive primary microcephaly type 3 (MCPH3) caused by pathogenic variations in CDK5RAP2, is characterized by sensorineural hearing loss, abnormality of skin pigmentation, ocular defects and severe microcephaly associated with neurodevelopmental delay. In this study, we expand the phenotype of MCPH3 as we describe a 10-year-old girl with a biallelic exonic frameshift variant in CDK5RAP2 displaying previously unreported features usually associated with Meier-Gorlin and microcephalic osteodysplastic primordial dwarfism type II (MOPDII). We further describe the clinical phenotype of this form of centrosomal-based primary microcephaly and emphasize the importance of skeletal defect screening in affected individuals.
由CDK5RAP2基因的致病性变异引起的常染色体隐性原发性小头畸形3型（MCPH3），其特征为感音神经性听力损失、皮肤色素沉着异常、眼部缺陷以及与神经发育迟缓相关的严重小头畸形。在本研究中，我们扩展了MCPH3的表型，因为我们描述了一名10岁女孩，其CDK5RAP2基因存在双等位基因外显子移码变异，表现出通常与Meier-Gorlin综合征和II型小头畸形骨发育异常原发性侏儒症（MOPDII）相关的先前未报道的特征。我们进一步描述了这种基于中心体的原发性小头畸形的临床表型，并强调了对受影响个体进行骨骼缺陷筛查的重要性。
