Behavior of scoliosis during growth in children with osteogenesis imperfecta.

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Abstract

[Indexed for MEDLINE] 19. Genes (Basel). 2022 Feb 24;13(3):407. doi: 10.3390/genes13030407. Phenotypic Variation in Vietnamese Osteogenesis Imperfecta Patients Sharing a Recessive P3H1 Pathogenic Variant. Zhytnik L(1)(2), Duy BH(3), Eekhoff M(4), Wisse L(1), Pals G(1), Reimann E(5), Kõks S(6)(7), Märtson A(2)(8), Maugeri A(1), Maasalu K(2)(8), Micha D(1). Author information: (1)Department of Human Genetics, Amsterdam Movement Sciences, Amsterdam UMC, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. (2)Department of Traumatology and Orthopaedics, Institute of Clinical Medicine, The University of Tartu, Puusepa 8, 50410 Tartu, Estonia. (3)Faculty of Nursing, College of Medicine and Pharmacy, Hue University, 06 Ngo Quyen, Hue 530000, Vietnam. (4)Amsterdam Bone Centre, Department of Internal Medicine Section Endocrinology, Amsterdam UMC, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. (5)Institute of Genomics, The University of Tartu, Riia 23b, 51010 Tartu, Estonia. (6)QEII Medical Centre, Perron, Institute for Neurological and Translational Science, 8 Verdun Street, Nedlands, WA 6009, Australia. (7)Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, 90 South Street, Murdoch, Perth, WA 6150, Australia. (8)Clinic of Traumatology and Orthopaedics, Tartu University Hospital, Puusepa 8, 50410 Tartu, Estonia. Osteogenesis imperfecta (OI) is a syndromic disorder of bone fragility with high variation in its clinical presentation. Equally variable is molecular aetiology; recessive forms are caused by approximately 20 different genes, many of which are directly implicated in collagen type I biosynthesis. Biallelic variants in prolyl 3-hydroxylase 1 (P3H1) are known to cause severe OI by affecting the competence of the prolyl 3-hydroxylation—cartilage associated protein—peptidyl-prolyl cis-trans isomerase B (P3H1-CRTAP-CyPB) complex, which acts on the Pro986 residue of collagen type I α 1 (COL1A1) and Pro707 collagen type I α 2 (COL1A2) chains. The investigation of an OI cohort of 146 patients in Vietnam identified 14 families with P3H1 variants. The c.1170+5G>C variant was found to be very prevalent (12/14) and accounted for 10.3% of the Vietnamese OI cohort. New P3H1 variants were also identified in this population. Interestingly, the c.1170+5G>C variants were found in families with the severe clinical Sillence types 2 and 3 but also the milder types 1 and 4. This is the first time that OI type 1 is reported in patients with P3H1 variants expanding the clinical spectrum. Patients with a homozygous c.1170+5G>C variant shared severe progressively deforming OI type 3: bowed long bones, deformities of ribcage, long phalanges and hands, bluish sclera, brachycephaly, and early intrauterine fractures. Although it remains unclear if the c.1170+5G>C variant constitutes a founder mutation in the Vietnamese population, its prevalence makes it valuable for the molecular diagnosis of OI in patients of the Kinh ethnicity. Our study provides insight into the clinical and genetic variation of P3H1-related OI in the Vietnamese population. DOI: 10.3390/genes13030407 PMCID: PMC8950175