Search Our Scientific Publications & Authors

Global Spine J 2021 Feb 18:2192568221994786. Epub 2021 Feb 18.

Hospital for Special Surgery, New York, NY, USA.

Study Design: Retrospective case series.

Objective: To report contemporary rates of complications and subsequent surgery after spinal surgery in patients with skeletal dysplasia.

Methods: A case series of 25 consecutive patients who underwent spinal surgery between 2007 and 2017 were identified from a single institution's skeletal dysplasia registry. Read More

Biochem Pharmacol 2021 Mar 3;185:114452. Epub 2021 Feb 3.

Department of Molecular Medicine, Unit of Biochemistry, University of Pavia, 27100 Pavia, Italy. Electronic address:

Diastrophic dysplasia (DTD) is a recessive chondrodysplasia caused by mutations in the SLC26A2 gene encoding for a sulfate/chloride transporter. When SLC26A2 is impaired intracellular level of sulfate is reduced leading to the synthesis of undersulfated proteoglycans. In normal chondrocytes, the main source of intracellular sulfate is the extracellular uptake through SLC26A2, but a small amount comes from the catabolism of sulfur-containing amino acids and other thiols. Read More

Spine Deform 2021 May 19;9(3):841-849. Epub 2021 Jan 19.

Department of Orthopaedic Surgery, The Children's Hospital at Westmead, Sydney, NSW, Australia.

Purpose: To trial the use of three-dimensional (3D) printed skull models to guide safe pin placement in two patients with diastrophic dysplasia (DTD) requiring prolonged pre-fusion halo-gravity traction (HGT).

Methods: Two sisters aged 8 (ML) and 4 (BL) with DTD were planned for staged fusion for progressive kyphoscoliosis. Both sisters were admitted for pre-fusion HGT. Read More

Diagnostics (Basel) 2020 May 7;10(5). Epub 2020 May 7.

Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan.

Skeletal dysplasia (SD) is a complex group of bone and cartilage disorders often detectable by fetal ultrasound, but the definitive diagnosis remains challenging because the phenotypes are highly variable and often overlap among different disorders. The molecular mechanisms underlying this condition are also diverse. Hundreds of genes are involved in the pathogenesis of SD, but most of them are yet to be elucidated, rendering genotyping almost infeasible except those most common such as fibroblast growth factor receptor 3 (), collagen type I alpha 1 chain (), collagen type I alpha 2 chain (), diastrophic dysplasia sulfate transporter (), and SRY-box 9 (). Read More

Eur J Med Genet 2019 Nov 10;62(11):103573. Epub 2018 Nov 10.

Folkhälsan Institute of Genetics and University of Helsinki, Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. Electronic address:

Pathogenic sequence variants in the solute carrier family 26 member 2 (SLC26A2) gene result in lethal (achondrogenesis Ib and atelosteogenesis II) and non-lethal (diastrophic dysplasia and recessive multiple epiphyseal dysplasia, rMED) chondrodysplasias. We report on two new patients with rMED and very rare compound heterozygous mutation combinations in non-consanguineous families. Patient I presented in childhood with waddling gait and joint stiffness. Read More

J Pharm Sci 2017 12 19;106(12):3631-3641. Epub 2017 Aug 19.

Department of Drug Science, University of Pavia, V.le Taramelli 115, Pavia 27100, Italy. Electronic address:

Potential off-label therapeutic role of N-acetylcysteine (N-Ac) was recently demonstrated in the treatment of diastrophic dysplasia (DTD) using mutant mice; its main drawback is the rapid clearance from blood due to the liver metabolism. Our goal was to investigate the potential of polyethylene glycol polylactide-co-glycolide block copolymer (PLGA-PEG)-based nanoparticles (NPs) in order to improve in vivo biodistribution performances and N-Ac pharmacokinetic profile after subcutaneous administration in mice. Results suggest that N-Ac can be effectively loaded into NPs (about 99 μg/mg NPs) using a suitably optimized nanoprecipitation method. Read More

Qual Life Res 2017 05 19;26(5):1337-1348. Epub 2016 Nov 19.

Department of Surgery, Center for Surgery and Public Health, Brigham & Women's Hospital, Harvard Medical School, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Introduction: Numerous factors associate with health disparities. The extent to which such factors influence health-related quality of life (HRQOL) among adults with short stature skeletal dysplasias (SD) is unknown. In an effort to update and clarify knowledge about the HRQOL of adults with SD, this study aimed to quantify HRQOL scores relative to the American average and assess whether specific indicators are associated with lower scores. Read More

J Craniovertebr Junction Spine 2015 Oct-Dec;6(4):216-8

Department of Orthopaedic Surgery and Rehabilitation, Faculty of Medicine, Jagiellonian University, Zakopane, Poland.

Cervical kyphosis in diastrophic dysplasia (DTD) is a very dangerous deformity which may lead to compression of neural structures resulting in tetraplegia or even. Treatment of this deformity is usually surgical, but no long-term follow-up studies are presented in the literature. Authors present a case of two children with DTD who underwent anterior corpectomy due to severe cervical kyphosis. Read More

Biochem J 2016 Mar 3;473(5):615-26. Epub 2015 Dec 3.

Department of Biochemistry, University of Toronto, Toronto, ON, Canada, M5S 1A8

The human solute carrier 26 (SLC26) family of anion transporters consists of ten members that are found in various organs in the body including the stomach, intestine, kidney, thyroid and ear where they transport anions including bicarbonate, chloride and sulfate, typically in an exchange mode. Mutations in these genes cause a plethora of diseases such as diastrophic dysplasia affecting sulfate uptake into chondrocytes (SLC26A2), congenital chloride-losing diarrhoea (SLC26A3) affecting chloride secretion in the intestine and Pendred's syndrome (SLC26A4) resulting in hearing loss. To understand how these mutations affect the structures of the SLC26 membrane proteins and their ability to function properly, 12 human disease-causing mutants from SLC26A2, SLC26A3 and SLC26A4 were introduced into the equivalent sites of the sulfate transporter anti-sigma factor antagonist (STAS) domain of a bacterial homologue SLC26 protein DauA (YchM). Read More

J Pediatr Orthop 2016 Oct-Nov;36(7):709-14

Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE.

Background: The aim of this study was to describe the dynamic lower extremity alignment in children with diastrophic dysplasia (DD) by 3-dimensional gait analyses. Our main hypothesis was that gait kinematics and kinetics are different than the age-normalized population and patellar dislocation can alter the gait in patients with DD.

Methods: A retrospective review of clinical data and radiographs was conducted for patients with DD who had gait analysis before lower extremity skeletal surgery excluding foot procedures. Read More

Hum Mol Genet 2015 Oct 23;24(19):5570-80. Epub 2015 Jul 23.

Department of Molecular Medicine, Unit of Biochemistry and

Diastrophic dysplasia (DTD) is a recessive chondrodysplasia caused by mutations in SLC26A2, a cell membrane sulfate-chloride antiporter. Sulfate uptake impairment results in low cytosolic sulfate, leading to cartilage proteoglycan (PG) undersulfation. In this work, we used the dtd mouse model to study the role of N-acetyl-l-cysteine (NAC), a well-known drug with antioxidant properties, as an intracellular sulfate source for macromolecular sulfation. Read More

A A Case Rep 2015 Jul;5(1):6-8

From the *Department of Anesthesiology, †Department of Otolaryngology, and ‡Department of Obstetrics and Gynecology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; and §Mountain West Anesthesia, Park City, Utah.

A 27-year-old primigravida patient with diastrophic dysplasia (DTD) presented to our obstetrics clinic at 8 weeks' gestational age. Diastrophic dysplasia is a rare, autosomal-recessive abnormality that presents multiple challenges to perinatal anesthetic management, including difficult airway management and relative contraindications to neuraxial anesthesia. The patient underwent elective cesarean delivery at 35 weeks' gestational age under general anesthesia. Read More

Proc Natl Acad Sci U S A 2015 Jun 15;112(26):8064-9. Epub 2015 Jun 15.

Institute of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an 710000, China;

Spondylolysis is a fracture in part of the vertebra with a reported prevalence of about 3-6% in the general population. Genetic etiology of this disorder remains unknown. The present study was aimed at identifying genomic mutations in patients with dysplastic spondylolysis as well as the potential pathogenesis of the abnormalities. Read More

Orthop Surg 2014 Nov;6(4):274-9

Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK, AUVA Trauma Centre Meidling, First Medical Department, Hanusch Hospital, Vienna, Austria; Paediatric Department, Orthopaedic Hospital of Speising, Vienna, Austria.

Objective: Accurate understanding of the cause of the underlying pathology in children with diastrophic dysplasia would help in designing targeted management of their locomotion.

Methods: Diastrophic dysplasia was diagnosed in twelve patients (nine girls and three boys; age range 1-14 years), all of whom presented with small stature and apparent short extremities. Club foot (mostly talipes equinovarus) was the most frequent and consistent abnormality. Read More

J Cell Sci 2014 Oct 21;127(Pt 20):4420-8. Epub 2014 Aug 21.

Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA

Mesenchymal cell condensation is the initiating event in endochondral bone formation. Cell condensation is followed by differentiation into chondrocytes, which is accompanied by induction of chondrogenic gene expression. Gene mutations involved in chondrogenesis cause chondrodysplasias and other skeletal defects. Read More

J Pediatr 2014 Jun 25;164(6):1493-4. Epub 2014 Mar 25.

Department of Pediatrics, Bangalore Medical College and Research Institute, Bangalore, India.

Indian Pediatr 2014 Feb;51(2):161

Department of Endocrinology and Metabolism, AIIMS, Ansari Nagar, New Delhi, India.

Clin Genet 2015 Mar 1;87(3):273-8. Epub 2014 Apr 1.

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden; Folkhälsan Institute of Genetics, Helsinki, Finland.

Diastrophic dysplasia (DTD) is an autosomal recessive skeletal dysplasia caused by SLC26A2 mutations. Clinical features include short stature, joint contractures, spinal deformities, and cleft palate. SLC26A2 mutations also result in other skeletal dysplasias, including the milder recessive multiple epiphyseal dysplasia (rMED). Read More

Hypertension 2014 May 3;63(5):1102-9. Epub 2014 Mar 3.

Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstr. 1, D-80336 Munich, Germany.

Elucidation of the molecular mechanisms leading to autonomous aldosterone secretion is a prerequisite to define potential targets and biomarkers in the context of primary aldosteronism. After a genome-wide association study with subjects from the population-based Cooperative Health Research in the Region of Augsburg F4 survey, we observed a highly significant association (P=6.78×10(-11)) between the aldosterone to renin ratio and a locus at 5q32. Read More

Int J Biochem Cell Biol 2014 Jul 14;52:58-67. Epub 2014 Feb 14.

INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France. Electronic address:

The solute carrier 26 (SLC26) proteins are transmembrane proteins located at the plasma membrane of the cells and transporting a variety of monovalent and divalent anions, including chloride, bicarbonate, sulfate and oxalate. In humans, 11 members have been identified (SLC26A1 to SLC26A11) and although part of them display a very restricted tissue expression pattern, altogether they are widely expressed in the epithelial cells of the body where they contribute to the composition and the pH regulation of the secreted fluids. Importantly, mutations in SLC26A2, A3, A4, and A5 have been associated with distinct human genetic recessive disorders (i. Read More

J Biol Chem 2014 Jan 3;289(4):1993-2001. Epub 2013 Dec 3.

From the Department of Biological Science, Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Republic of Korea.

Mutations in the SO4(2-)/Cl(-)/OH(-) exchanger Slc26a2 cause the disease diastrophic dysplasia (DTD), resulting in aberrant bone development and, therefore, skeletal deformities. DTD is commonly attributed to a lack of chondrocyte SO4(2-) uptake and proteoglycan sulfation. However, the skeletal phenotype of patients with DTD is typified by reduction in cartilage and osteoporosis of the long bones. Read More

J Pediatr Endocrinol Metab 2014 Jan;27(1-2):75-80

Background: Multiple epiphyseal dysplasia (MED) is one of the common hereditary osteochondrodysplasias. Mutations in diastrophic dysplasia sulfate transporter gene (DTDST) result in recessive MED.

Objective: To investigate the possible gene mutation in a recessive MED patient. Read More

Am J Med Genet A 2013 Aug 9;161A(8):2088-94. Epub 2013 Jul 9.

Department of Clinical Genetics, Hospital of Rehabilitation of Craniofacial Anomalies, University of São Paulo (HRAC/USP), Bauru, São Paulo, Brazil.

Mutations in solute carrier family 26 (sulfate transporter), member 2 (SLC26A2) gene result in a spectrum of autosomal recessive chondrodysplasias that range from the mildest recessive form of multiple epiphysial dysplasia (rMED) through the most common diastrophic dysplasia (DTD) to lethal atelosteogenesis type II and achondrogenesis IB. The clinical variability has been ascribed to quantitative effect of mutations of the sulfate transporter activity. Here we describe two Brazilian sisters, born to healthy and non consanguineous parents, with Robin sequence, mild shortening of upper and lower limbs, brachymetacarpalia/tarsalia, additional and accelerated carpal ossification, marked genu valgum, and multiple epiphysial dysplasia. Read More

Sao Paulo Med J 2013 ;131(2):127-32

Faculdades Integradas do Brasil UniBrasil, Curitiba, Paraná, Brazil.

Context: Diastrophic dysplasia is a type of osteochondrodysplasia caused by homozygous mutation in the gene DTDST (diastrophic dysplasia sulfate transporter gene). Abnormalities occurring particularly in the skeletal and cartilaginous system are typical of the disease, which has an incidence of 1 in 100,000 live births.

Case Report: The case of a pregnant woman, without any consanguineous relationship with her husband, whose fetus was diagnosed with skeletal dysplasia based on ultrasound findings and DNA tests, is described. Read More

Am J Med Genet A 2013 Jun 23;161A(6):1491-4. Epub 2013 Apr 23.

Department of Paediatric Orthopaedic Surgery, Turku University Central Hospital, Turku, Finland.

J Rehabil Med 2013 Mar;45(3):308-13

Orton Rehabilitation Centre, Orton Orthopaedic Hospital, Helsinki, Finland.

Objective: The purpose of the present study was to gain a comprehensive view of the quality of life and socio-economic conditions in a more representative sample of patients with diastrophic dysplasia than previously presented.

Methods: The study sample comprised 115 patients with diastrophic dysplasia, aged over 18 years. The patients were contacted, and 68 patients (59%) agreed to participate in the study. Read More

Bone 2013 May 28;54(1):83-91. Epub 2013 Jan 28.

Department of Molecular Medicine, Section of Biochemistry, University of Pavia, Pavia, Italy.

Diastrophic dysplasia (DTD) is a chondrodysplasia caused by mutations in the SLC26A2 gene, leading to reduced intracellular sulfate pool in chondrocytes, osteoblasts and fibroblasts. Hence, proteoglycans are undersulfated in the cartilage and bone of DTD patients. To characterize the bone phenotype of this skeletal dysplasia we used the Slc26a2 knock-in mouse (dtd mouse), that was previously validated as an animal model of DTD in humans. Read More

Am J Med Genet A 2012 Jul 24;158A(7):1551-5. Epub 2012 May 24.

Department of Otolaryngology-Head and Neck Surgery, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland 21287-0910, USA.

A hearing screening program was performed to determine the prevalence of hearing loss and abnormal tympanometry in individuals with short-stature skeletal dysplasias attending a national meeting. Behavioral audiometry, otoacoustic emission testing, and tympanometry were used to assess hearing. Failed hearing screen was defined as hearing ≥ 35 dB at one or more frequencies or by "fail" on otoacoustic emissions. Read More