Aberrant Pax1 and Pax9 expression in Jarcho-Levin syndrome: report of two Caucasian siblings and literature review.
We report two consecutive Caucasian male siblings of nonconsanguineous parents autopsied at 22 and 13 weeks gestational age both with prenatal diagnosis of Jarcho-Levin syndrome (JLS). Segmentation anomalies of the vertebrae and ribs encompass a spectrum of syndromes with or without associated anomalies of other developmental fields, and include spondylothoracic dysostosis (STD), JLS, Casamassima-Morton-Nance (CMN) syndrome, and spondylocostal dysostosis (SCD), among others. In both these new JLS cases the autopsies confirmed that there were severe developmental alterations in the thoracic and vertebral skeleton (including "crab-like" thorax), accompanied in the older fetus by renal defects. Because vertebral development is controlled by a limited number of master genes including Pax1 and Pax9, we analyzed protein expression from these genes in these two cases compared to age-matched controls. Immunochemical analysis showed a significant reduction in levels of Pax1 and Pax9 protein expression in chondrocytes of the vertebral column. Implications for the etiology and pathogenesis of JLS and related disorders are discussed.
Bannykh
Sergei I
SI
Department of Pathology, University of California, San Diego-Medical Center, San Diego, California 92103-8321, USA.
Emery
Shawn Clark
SC
Gerber
Josef-Karl
JK
Jones
Kenneth L
KL
Benirschke
Kurt
K
Masliah
Eliezer
E
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004413:Dysostoses / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D005260:Female; D005313:Fetal Death; D006801:Humans; D007668:Kidney / Q000473:pathology; D008297:Male; D009139:Musculoskeletal Abnormalities / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D010375:Pedigree; D011247:Pregnancy; D011859:Radiography; D035781:Siblings; D013577:Syndrome; D013904:Thoracic Vertebrae / Q000002:abnormalities / Q000000981:diagnostic imaging; D016216:Ultrasonography, Prenatal
D004268:DNA-Binding Proteins