Peng Hsiu-Huei, Kuo Pao-Lin, Chao An-Shine, Wang Tzu-Hao, Chang Yao-Lung, Soong Yung-Kuei, Chang Shuenn-Dyh
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Lin-ko Medical Center, Tao-Yuan, Taiwan.
Fetal Diagn Ther. 2007;22(5):389-93. doi: 10.1159/000103302. Epub 2007 Jun 5.
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).
我们报告一名30岁双胎妊娠女性，在妊娠23周时超声检查发现1个胎儿头围小、半侧叶全前脑畸形及唇裂。胎儿磁共振成像确诊为半侧叶全前脑畸形。然而，另一个胎儿生长发育正常，无任何主要结构异常。对两个胎儿的羊水穿刺标本进行G显带核型分析显示为47,XY,+mar。荧光原位杂交显示，标记染色体上15号染色体着丝粒特异性α卫星DNA探针（D15Z1）呈阳性双着丝粒信号，而SNRPN探针（15q11 - 13）呈阴性信号，从而确定两个胎儿的细胞遗传学诊断均为47,XX,+mar.ish idic(15)(q11 - q13)(D15Z1++,SNRPN-)。父母的核型正常。因此，胎儿有一条新发的inv dup(15)标记染色体，且普拉德-威利区域未受累。短串联重复标记（共15个标记）证实胎儿为单卵双胎。15q区域的短串联重复标记（共6个标记）排除了母源性单亲二体（15）或父源性单亲二体（15）的可能性。对两个胎儿的TGIF、SHH、SIX3和ZIC2基因进行分子研究发现，SHH基因存在杂合的1085 C > T（Ser 362 Leu）突变，但父母的SHH基因均为纯合的1085 C > C（Ser 362 Ser）。这对夫妇决定在妊娠26周时终止妊娠。据我们所知，这是首例伴有inv dup(15)标记染色体和错义SHH基因突变1085 C > T（Ser 362 Leu）的半侧叶全前脑畸形报告。
