Balkan Journal of Medical Genetics

SLC26A2 RELATED DIASTROPHIC DYSPLASIA IN 42-YEARS UKRAINIAN WOMEN
Bondarenko M.1, Haiboniuk I.2,3, Solovei I.4, Shargorodska Y.2, Makukh H.2, 3*
*Corresponding Author: *Corresponding Author: Makukh Halyna, Ph.D., 31-A Lysenko Institute of Hereditary Pathology of the Ukrainian National Academy of Medical Sciences, Lviv, Ukraine, & Scientific Medical Genetic Center LeoGENE, Maksymovych, 7g str, Lviv, Ukraine, 79059. Tel +380677191380, E-mail: mgdc@leogene.com.ua
page: 83

INTRODUCTION

Diastrophic dysplasia (DTD), or diastrophic dwarfism, is an uncommon genetic pathology falling under the group of skeletal dysplasias [1]. It is a progressive condition conducting to physical disability [2]. The first signs of DTD are observed at birth and develop following the defects in cartilage buildup process, affecting skeletal formation. Additionally, respiratory complications may lead to increased mortality in children with DTD in the neonatal period [3]. The associated symptomatic findings include their severity and range, showing a wide diversity in separate cases. Concurrently, the clinical features often include limb shortening (short-limbed dwarfism) and short stature; defective development of joints (joint dysplasia) and bone structure (skeletal dysplasia) in many body regions; progressive pathological spine curvature (predominantly scoliosis and/or kyphosis); pathological changes in the pinnae tissue (external ear parts); they may also include craniofacial area malformations [4, 9, 11, 21]. IQ is usually normal. The diagnosis is based on the presence of pathogenic variants in SLC26A2, which is associated with autosomal recessive forms of skeletal dysplasia, in pair with phenotypic symptoms and radiographic findings [5]. Confirmation of diagnosis during the prenatal period can be executed by ultrasound and an invasive prenatal diagnostic with a molecular genetic testing [6]. More than 300 genes were reported to be involved in skeletal dysplasia with autosomal recessive (AR), autosomal dominant and X-linked manner (Table 1). Clinical signs of all these diseases have similar manifestations and a comparable phenotype, thus only genetic testing results can state the appropriate diagnosis and determine the disorder risk for relatives. The type of inheritance and are presented in the Table 1. The prevalent skeletal dysplasia type is FGFR3-related disorders, inherited in an autosomal-dominant manner [6]. Diastrophic dysplasia occurs predominantly among the Caucasian population [3, 8]. The prevalence of DTD is estimated at 1-1.3/100,000, and mainly has an AR type of inheritance. The disorder affects both males and females in equal numbers [4]. This pathology is widespread in Finland, occurring in about 1 in 30,000 newborns. In particular, 1-2% of the Finnish population are carriers of pathogenic variants of the SLC26A2 gene [14]. Mutations in this gene demonstrate a very diverse clinical spectrum. 183 cases of DTD have been diagnosed and described in Finland. Frequency of occurrence of this disorder in our country is unknown. Several cases of FGFR3-related condition have been reported among Ukrainian patients, but there are no reliable data on the prevalence of skeletal dystrophy with other types of inheritance. We present this case report of DTD in a 42-year-old Ukrainian woman, whose DTD is caused by SLC26A2 gene biallelic pathogenic variants. Mutation in the SLC26A2 gene (otherwise known as the Diastrophic Dysplasia Sulfate Transporter (DDST) gene) is to be found on the long arm of chromosome 5 (5q32-q33.1) [https://www.genecards.org/cgi-bin/carddisp. pl?gene=SLC26A2] and leads to the occurrence of diastrophic dysplasia and other skeletal dysplasias with a diverse clinical gravity. The SLC26A2 gene is responsible for protein that transports sulfate ions across cell membranes, being necessary for the formation of proteoglycans. Proteoglycans help provide cartilage with its consistency. Since sulfate ion particles are necessary for the formation of proteoglycans, the activity of the SLC26A2 protein is fundamental for cartilage development [7, 12]. SLC26A2 gene mutations that cause diastrophic dysplasia (described more than 20 mutations [7, 8]) lead to a deficiency of sulfate ions. Therefore, the normal formation of cartilage and bone growth are disturbed [13, 14, 16]. The most frequently occurring variants are p.Arg279Trp (ratio in the disease alleles is 37%), p.Arg178Ter, c.- 26+2T>C and p.Cys653Ser (13, 8 and 6%, respectively). Other pathogenic variants are at ≤3% each. Compound heterozygous pathogenic variants are reported in most cases of DTD (97%) [17, 18]. Taking into the account the rareness of the disease, ethnic difference, and the lack of reporting about DTD disease course in adults, we present the phenotype description of 42-year-old woman from the west of Ukraine with diastrophic dysplasia and two pathogenic variants in the SLC26A2 gene.

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