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

CASE REPORT

We present a case of DTD in a 42-year-old Ukrainian woman. The patient’s stature is 110 cm with S-shaped deformation of the spine. The patient’s daughter applied to the Medical Genetic Center for advice on pregnancy planning and the possible risk of skeletal dysplasia for future children. The daughter is clinically healthy. The anamnesis and result of examination of her mother with skeletal dysplasia is as follows: she has been patient from a physiological birth. Her birth weight was 4,200 kg. After birth, the newborn was diagnosed with severe asphyxia. The parents of the woman are somatically healthy, and they are not closely related. No cases of skeletal dysplasia in the family have been reported. The patient also had stridor nasal breathing at birth. The phenotype of the patient had the following features: the lower extremities were poorly stretched and tight to the body. The conclusion of the orthopedist during the examination was that the shortening of long (tubular) bones were manifested more on the lower extremities. At the age of 1 year the diagnosis was congenital dislocation of a hip, bilateral; arthrogryposis. At age of 21, she was diagnosed with a mixed form of chronic cholecystitis. At the age of 23, she was diagnosed with left ureter contraction, urolithiasis, chronic gastritis, kyphoscoliosis. At the age of 24, she was diagnosed with spondyloepiphyseal dysplasia, obsolete injury of the left shoulder. The woman was referred for consultation to the Institute of Traumatology and Orthopedics, where she was diagnosed with multiple skeletal bone deformities . They recommended to perform an MRI to assess skeletal bone damage. The MRI findings showed scoliosis (4th grade), osteochondrosis, spondyloarthritis of the spine. There were also protrusions of disks C3-C4, C4-C5, C5-C6, C6-C7, and L5-S1 (Figure 1). Intervertebral space contracted from L1 to L5 (Figure 1). The patient has the skull of normal size with a disproportionately short skeleton, short lower extremities, brachydactylia, lack of interphalangeal creases, and hitch diagnosed with multiple skeletal bone deformities . They recommended to perform an MRI to assess skeletal bone damage. The MRI findings showed scoliosis (4th grade), osteochondrosis, spondyloarthritis of the spine. There were also protrusions of disks C3-C4, C4-C5, C5-C6, C6-C7, and L5-S1 (Figure 1). Intervertebral space contracted from L1 to L5 (Figure 1). The patient has the skull of normal size with a disproportionately short skeleton, short lower extremities, brachydactylia, lack of interphalangeal creases, and hitchhiker thumb (abduced, located proximally) (Figures 2, 3, 4). The patient also has a vision defect, specifically myopia. Deviations in intellectual development were not observed. She has two healthy children born by caesarean section. Due to the observed phenotype and skeletal deformities, the genetic testing of the panel genes involved in the etiology of skeletal disorders was performed by the next generation sequencing (NGS) method. The selected diagnostic test evaluates complete sequencing and deletion/ duplication of 320 genes (Appendix 1) for variants, which are associated with genetic disorders that have phenotype of skeletal dysplasia. Two pathogenic variants in the SLC26A2 gene and two variants with uncertain value were revealed in the patient. The SLC26A2 gene mutations c.1020_1022del (p.Val341del) and c.1957T>A (p.Cys653Ser) were confirmed. In LTBP2 gene, a Variant of Uncertain Significance, or c.3913G>C (p.Asp1305His), was identified. The LTBP2 gene is related to microspherophakia and autosomal recessive primary congenital glaucoma (PCG). The LTBP2 gene also shows preliminary evidence asserting association with autosomal recessive Marfan-like syndrome and autosomal recessive type 3 Weill-Marchesani syndrome (WMS). In the TTC21B gene, a Variant of Uncertain Significance, c.3932G>A (p.Arg1311His), was identified. The TTC21B gene correlates with asphyxiating thoracic dystrophy and autosomal recessive nephronophthisis. (Table 2) Two pathogenic variants, c.1020_1022del (p.Val341del) and c.1957T>A (p.Cys653Ser), were identified in SLC26A2, and the diagnosis of diastrophic dysplasia was confirmed. This condition has an autosomal-recessive manner of inheritance. Two descendants of the patient had normal phenotypes and both were heterozygous carriers of the mutation. SLC26A2 mutation testing for future partners was recommended during the medical-genetic consultation.

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