Paper

Discordant Semilobar Holoprosencephaly in Monozygotic Twins with de novo inv dup(15) Marker Chromosome and de novo Mutation on SHH Gene
Hsiu-Huei Peng^{a, d}, Pao-Lin Kuo^c, An-Shine Chao^{a, d}, Tzu-Hao Wang^{a, b, d}, Yao-Lung Chang^{a, d}, Yung-Kuei Soong^{a, d}, Shuenn-Dyh Chang<sup>a, d

a</sup>Department of Obstetrics and Gynecology and
^bCenter of Genomics, Chang Gung Memorial Hospital, Lin-ko Medical Center, Tao-Yuan,
^cDivision of Genetics, Department of Obstetrics and Gynecology, National Cheng-Kung University Medical Center, Tainan, and
^dChang Gung University College of Medicine, Tao-Yuan, Taiwan

Address of Corresponding Author

Fetal Diagn Ther 2007;22:389-393 (DOI: 10.1159/000103302)

  Key Words

• Semilobar holoprosencephaly
• Inv dup(15) marker chromosome
• SHH gene mutation

  Abstract

We present a 30-year-old woman with a twin pregnancy, 1 fetus displaying a small head circumference, semilobar holoprosencephaly, and cleft lip as detected by ultrasound at 23 weeks of gestation. Fetal magnetic resonance imaging confirmed the diagnosis of semilobar holoprosencephaly. The other twin, however, had an appropriate fetal growth, devoid of any major structural anomalies. Karyotyping by G-banding of amniocentesis specimens in both fetuses showed 47,XY,+mar. Fluorescence in situ hybridization showed in the marker chromosome positive dicentric signals for the chromosome 15 centromere-specific alpha satellite DNA probe (D15Z1) and negative signals for the SNRPN probe (15q11-13), thus establishing a cytogenetic diagnosis of 47,XX,+mar.ish idic(15)(q11-q13)(D15Z1++,SNRPN-) for both fetuses. The parental karyotypes were normal. The fetuses, therefore, had a de novo inv dup(15) marker chromosome without involvement of the Prader-Willi region. Short tandem repeat markers (total 15 markers) confirmed that the fetuses were monozygotic twins. Short tandem repeat markers at the 15q region (total 6 markers) excluded the possibility of uniparental disomy (15) mat or uniparental disomy (15) pat. Molecular study in both fetuses of TGIF, SHH, SIX3, and ZIC2 genes revealed a heterozygous 1085 C > T (Ser 362 Leu) on the SHH gene, but a homozygous 1085 C > C (Ser 362 Ser) for both parents on the SHH gene. The couple decided to terminate the pregnancy at 26 weeks of gestation. To our knowledge, this is the first report of semilobar holoprosencephaly with inv dup(15) marker chromosome and missense SHH gene mutation 1085 C > T (Ser 362 Leu).

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Shuenn-Dyh Chang
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital 5 Fu-Hsing Street, Kwei-Shan
Tao-Yuan 333 (Taiwan)
Tel. +886 3 328 1200 8251, Fax +886 3 328 8252, E-Mail gene@cgmh.org.tw

  Article Information

Received: January 17, 2006
Accepted after revision: August 8, 2006
Published online: June 5, 2007
Number of Print Pages : 5
Number of Figures : 2, Number of Tables : 2, Number of References : 38