J Korean Med Sci.  2010 Jan;25(1):159-162. 10.3346/jkms.2010.25.1.159.

A Novel DHCR7 Mutation in a Smith-Lemli-Opitz Syndrome Infant Presenting with Neonatal Cholestasis

• Ko JS
• Choi BS
• Seo JK
• Shin JY
• Chae JH
• Kang GH
• Lee R
• Ki CS
• Kim JW

• KMID: 1713850
• DOI: http://doi.org/10.3346/jkms.2010.25.1.159

Abstract

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive malformation syndrome caused by a defect in cholesterol biosynthesis. The incidence is very low in Asians and only one case has been reported in Korea thus far. Recently, we found an infant with neonatal cholestasis. He had microcephaly, ambiguous genitalia, cleft palate, syndactyly of toes, patent ductus arteriosus and hypertrophic pyloric stenosis. The serum cholesterol was decreased and serum 7-dehydrocholesterol was markedly elevated. Genetic analysis of the DHCR7 gene identified a novel missense mutation (Pro227Ser) as well as a known mutation (Gly303Arg) previously identified in a Japanese patient with SLOS. Although rare in Korea, SLOS should be considered in the differential diagnosis of neonatal cholestasis, especially in patients with multiple congenital anomalies and low serum cholesterol levels.

Keyword

Smith-Lemli-Opitz Syndrome; Cholestasis; 7-dehydrocholesterol reductase; Mutation

MeSH Terms

Amino Acid Substitution
Base Sequence
Cholestasis/*diagnosis
Ductus Arteriosus, Patent/diagnosis
Electroencephalography
Humans
Infant, Newborn
Liver/pathology/ultrasonography
Male
*Mutation, Missense
Oxidoreductases Acting on CH-CH Group Donors/*genetics
Phenotype
Smith-Lemli-Opitz Syndrome/diagnosis/*genetics
Oxidoreductases Acting on CH-CH Group Donors

Figure

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  Fig. 1 Percutaneous liver biopsy exhibited ballooning or feathery degeneration and macrovesicular fat droplets in lobular hepatocytes and periportal fibrosis and ductular proliferation in a portal space.

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  Fig. 2 (A) Direct sequencing of the DHCR7 gene. A novel missense mutation (c.679C>T; Pro227Ser) was identified in the patient and his mother (filled arrow) and a known mutation was found in the patient and his father (open arrow). (B) The Pro227Ser mutation was evolutionary conserved residue among different species. (http://www.ncbi.nlm.nih.gov/sites/entrez?db=protein)

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