Prenatal diagnosis of familial transmission of 17q12 microduplication associated with no apparent phenotypic abnormality

Chen, Chih‐Ping; Fu, Chung Hu; Lin, Yi Hui; Chern, Schu‐Rern; Wu, Peih Shan; Chen, Yen Ni; Chen, Shin Wen; Wang, Wayseen

doi:10.1016/j.tjog.2016.08.004

Cited by 5 publications

(7 citation statements)

References 16 publications

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“…These data suggest that mild ventriculomegaly and agenesis of the corpus callosum in the fetal ultrasound phenotype may also be indicators of the 17q12 microduplication syndrome. In contrast, Chen et al had reported the absence of obvious ultrasound abnormalities in a fetus with the 17q12 microduplication syndrome (26). This is in accordance to the normal ultrasound phenotype we observed in our study.…”

Section: Discussionsupporting

confidence: 92%

“…In this study, the microduplication region was found to contain 15 OMIM genes, including HNF1B (189907), LHX1 (601999), CCL4L1 (603782), CCL4L2 (610757), and CCL3L1 (601395), among which HNF1B is the most closely related to the disease ( 26 – 31 ). The HNF1B gene is mostly associated with kidney disorders, followed by neurodevelopmental disorders ( 18 , 32 – 34 ).…”

Section: Discussionmentioning

confidence: 90%

“…This incomplete penetrance and variable expression, possibly involving phenotypes with neurodevelopmental disorders, presents challenges to prenatal counseling and phenotype prediction after birth. The 17q12 microduplication syndrome is 90% inherited by autosomal dominance from the least affected parent or the parent with a normal phenotype ( 26 ). The microduplication of the 17q12 region in two fetuses in this study was pedigree verified to be inherited from a parent with a normal phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…The fetal ultrasound phenotypes reported in our study enrich the clinical database, given that the clinical phenotypes of the 17q12 microduplication syndrome are complex and diverse, requiring large sample data and more in-depth clinical studies. In this study, the microduplication region was found to contain 15 OMIM genes, including HNF1B (189907), LHX1 (601999), CCL4L1 (603782), CCL4L2 (610757), and CCL3L1 (601395), among which HNF1B is the most closely related to the disease (26)(27)(28)(29)(30)(31). The HNF1B gene is mostly associated with kidney disorders, followed by neurodevelopmental disorders (18,(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

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Prenatal ultrasound phenotypic and genetic etiology of the 17q12 microduplication syndrome

et al. 2022

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BackgroundSeveral studies have reported on the clinical phenotype of the 17q12 microduplication syndrome, a rare autosomal dominant genetic disorder, in children and adults, but few have reported on its prenatal diagnosis. This study analyzed the prenatal ultrasound phenotypes of the 17q12 microduplication syndrome to improve the understanding, diagnosis, and monitoring of this disease in fetuses.MethodsA retrospective analysis of 8,200 pregnant women who had received an invasive antenatal diagnosis at tertiary referral hospitals between January 2016 and August 2021 was performed. Amniotic fluid or cord blood was sampled from the pregnant women for karyotyping and chromosome microarray analysis (CMA).ResultsThe CMA revealed microduplication in the 17q12 region of the genome in five fetuses, involving fragments of about 1.5–1.9 Mb. Five fetuses with the 17q12 microduplication syndrome had different prenatal ultrasound phenotypes, including duodenal obstruction (two fetuses); mild ventriculomegaly, dysplasia of the septum pellucidum, agenesis of the corpus callosum (one fetus); and a strong echo in the left ventricle only (one fetus). The ultrasound phenotype of one fetus was normal. Among the five fetuses with the 17q12 microduplication syndrome, the parents of three refused CNV segregation analysis, while CNV segregation analysis was performed for the remaining two fetuses to confirm whether the disorder was inherited maternally or paternally, with normal phenotypes. After genetic counseling, the parents of those two fetuses chose to terminate the pregnancy, while the parents of the three unverified fetuses continued the pregnancy, with normal follow-up after birth.ConclusionAlthough prenatal ultrasound phenotypes in fetuses with the 17q12 microduplication syndrome are highly variable, our study has highlighted the distinct association between duodenal obstruction and the 17q12 microduplication syndrome. Understanding the relationship between the pathogenesis of the 17q12 microduplication in prenatal ultrasound phenotypes and its long-term prognosis will contribute to better genetic counseling concerning the 17q12 microduplication syndrome, which is still a challenge.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Prenatal ultrasound phenotypic and genetic etiology of the 17q12 microduplication syndrome

et al. 2022

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“…The clinical features include renal cysts, diabetes of the young type 5(MODY5) [5–7], Mullerian aplasia, dysgenesis [8, 9], autism spectrum disorder schizophrenia [10, 11], learning difficulties, speech delay, neonatal cholestasis, and transient neonatal hypercalcemia [12]. The main clinical manifestations of chromosome 17q12 microduplication syndrome (OMIM 614526) are developmental delay, brain dysplasia, epilepsy, cognitive impairment, and behavioral abnormalities [13]. Less common phenotypes include esophageal atresia, eye abnormalities, cleft palate, heart defects, and sex reversal [14].…”

Section: Introductionmentioning

confidence: 99%

Prenatal diagnosis of 17q12 microdeletion and microduplication syndrome in fetuses with congenital renal abnormalities

et al. 2019

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Background Copy number variations (CNVs) involving the 17q12 region are associated with a broad range of clinical phenotypes. Deletion of the 17q12 chromosome results in structural or functional abnormalities in the kidney and urethra, type 5 diabetes (MODY5), and neurodevelopmental or neuropsychiatric disorders. Microduplication of 17q12 is rare and is associated with an increased risk of epilepsy and mental retardation. We studied the prenatal diagnosis of 17q12 microduplication and microdeletion syndrome in fetuses with congenital renal abnormalities. Case presentation We conducted a retrospective analysis of prenatal diagnoses in our hospital from January 2016 to April 2018. Abnormal renal ultrasound findings were present in 126 fetuses and the incidence of chromosomal abnormalities was 10.32%(13/126). Conventional karyotyping detected 7 of 126 fetuses as aneuploid (5.56%). In addition, chromosome microarray analysis (CMA) detected 6 fetuses(4.76%) with copy number variations (CNVs), of which 5 were shown to have 17q12 microdeletion syndrome and 1 had 17q12 microduplication syndrome. We followed up these pregnant women. The results of the testing had a significant impact on pregnancy outcome. The phenotypes of 17q12 microdeletions and microduplications vary widely, affecting patients in different ways, such as language delays, social deficiencies, and even abortion. Conclusions The characteristics of 17q12 microdeletions and microduplications are so vague that the condition is often misdiagnosed or missed. This study demonstrated that karyotype analysis combined with CMA can significantly improve the diagnostic rate in prenatal diagnosis of CNVs, which can provide evidence for genetic counseling in such pregnancies.

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Road to a rare diagnosis: Description of novel unbalanced translocation causing partial trisomy 17p

Musabi

Saker

Baer

et al. 2022

Clinical Case Reports

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Trisomy 17 is a rare chromosomal disorder. Existing literature on the topic is limited and mostly refer to mosaic Trisomy 17 cases. Our report summarizes the 70‐day clinical course of a late preterm neonate with partial Trisomy 17p karyotype 46,XY,der(14)t(14;17)(p11.1;p11.2) dpat. Trisomy 17 due to unbalanced translocation is rare, and our case elaborates the clinical presentation with intestinal malfunction without any anatomical pathology and urethral diverticulum and the ethical dilemma in decision‐making. The male proband was born at 35 weeks with antenatal findings of multiple neurological and other abnormalities such as cystic hygroma, absent corpus collosum, high riding third ventricle, absent cavum septum pellucidum, indented occiput, absent ductus venous, and intrauterine growth restriction. The postnatal findings included significant facial dysmorphisms with short palpebral fissures, hypertelorism, low set ears, micrognathia, hirsutism, and single palmar creases, central hypotonia, and hyperreflexia of upper limbs bilaterally. Genital‐urinary assessment revealed a urinary diverticulum and significantly underdeveloped scrotum with undescended testes. Infant had excessive irritability and resistance to sleep despite increasing doses of analgesia and sedation, and persistent respiratory and feeding difficulties. Enteral nutrition could not be established due to profuse and persistent diarrhea, necessitating use of total parenteral nutrition. Microarray assay exhibited a pathogenic copy number gain of approximately 21.4 Mb of chromosome region 17p13.3p11.2. Follow‐up chromosome analysis and FISH revealed an abnormal male karyotype with a derivative chromosome 14, resulting from an unbalanced translocation between the short arm of one chromosome 14 and the short arm of one chromosome 17, effectively resulting in trisomy 17p11.2. It was derived from a paternal balanced t(14;17)(p11.1;p11.2) as shown by chromosome analysis and FISH studies. The rarity of this chromosomal disorder contributed to difficulty with prognosis and led to bioethical dilemma regarding life‐sustaining measures and quality of life. Through shared decision‐making processes and in consideration of poor prognosis, parents decided to withdraw life‐sustaining care and the proband died at postnatal day of life 70.

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Prenatal diagnosis of familial transmission of 17q12 microduplication associated with no apparent phenotypic abnormality

Abstract: The 17q12 microduplication may present with variable phenotypes including no apparent phenotypic abnormality in familial cases. However, neuropsychiatry assessment and monitoring should be warranted in childhood and through adulthood under such a circumstance.

Cited by 5 publications

References 16 publications

Prenatal ultrasound phenotypic and genetic etiology of the 17q12 microduplication syndrome

Prenatal ultrasound phenotypic and genetic etiology of the 17q12 microduplication syndrome

Prenatal diagnosis of 17q12 microdeletion and microduplication syndrome in fetuses with congenital renal abnormalities

Road to a rare diagnosis: Description of novel unbalanced translocation causing partial trisomy 17p

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