Johanson-Blizzard syndrome with mild phenotypic features confirmed by UBR1 gene testing

Abstract

Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive condition associated with exocrine pancreatic insufficiency, and is characterized by hypoplastic nasal alae, mental retardation, sensorineural hearing loss, short stature, scalp defects, dental abnormalities and abnormal hair patterns. Growth hormone deficiency, hypopituitarism, and impaired glucagon secretion response to insulin-induced hypoglycemia have been reported. Congenital heart defects have also been described in this condition. Mental retardation is typically moderate to severe in patients with JBS; however, normal intelligence can occur. In the pancreas, there is a selective defect of acinar tissue, whereas the islets of Langerhans and ducts are preserved. Diabetes has been reported in older children, suggesting the progressive nature of pancreatic disease. The molecular basis of JBS has recently been mapped to chromosome 15q15-q21 with identified mutations in the UBR1 gene. We report the case of a 7-year-old female with pancreatic insufficiency and mild phenotypic features, in whom the diagnosis of JBS was established using recently described molecular testing for the UBR1 gene.

Johanson-Blizzard Syndrome with Short Stature

“…Varying degrees of decreased secre on of lipases, pancrea c juices such as trypsin, trypsinogen and others, as well as malabsorp on of fats and disrup ons of glucagon secre on and its response to hypoglycemia caused by insulin ac vity are major concerns when JBS is diagnosed 1,3,8 . Pancrea c exocrine insuffi ciency in JBS can addi onally stem from congenital replacement of the acini with fa y ssue 1,3,8,9 .…”

“…Pancrea c exocrine insuffi ciency in JBS can addi onally stem from congenital replacement of the acini with fa y ssue 1,3,8,9 . Near total replacement of the en re pancreas with fa y ssue has also been reported.…”

“…It was named a er Ann J Johanson and Robert M Blizzard. The paediatricians who fi rst described the disorder in a 1971 1,2,3 .…”

Стеатоз Підшлункової Залози В Дітей. Частина 1. Етіологія, Епідеміологія Та Патогенез

“…Даний синдром викликається мута-ціями в гені UBR1, що кодує один із декількох фермен-тів убіквітинлігази. Екзокринна недостатність ПЗ при синдромі JBS може додатково бути наслідком вродже-ної заміни ацинусів жировою тканиною [18]. Гастроентерологія, p-ISSN 2308-2097, e-ISSN 2518-7880…”

Clinical utility gene card for: Johanson–Blizzard syndrome

“…Fifty-nine different mutations are known (including published mutations [1][2][3][4][5][6][7][8] and unpublished mutations identified in our lab). These include nonsense mutations (15), splice site mutations (14), small deletions and duplications/insertions causing frameshift (9), small inframe deletions (3) and missense mutations (18).…”