14q22.3 Microdeletion encompassing <i>OTX2</i> in a five-generation family with microphthalmia, pituitary abnormalities, and intellectual disability

Jones, Gabriela; Robertson, Lisa; Warman, Paul; Craft, Emily; Cresswell, Lara; Vasudevan, Pradeep

doi:10.3109/13816810.2015.1059463

Cited by 5 publications

(4 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, duplications involving this gene have been previously related to OAVS (Ballesta-Martínez et al, 2013). Even though OTX2 is associated with ocular anomalies, such as microphthalmia and anophthalmia (Jones et al, 2016;Lonero et al, 2016;Shimada, Takagi, Nagashima, Miyai, & Hasegawa, 2016;Slavotinek et al, 2015), our patient (P4) does not present ocular alterations. CNVs encompassing these genes identified in Brazilian patients from Bragagnolo et al (2018).…”

Section: Discussionmentioning

confidence: 62%

Rare single‐nucleotide variants in oculo‐auriculo‐vertebral spectrum (OAVS)

Zamariolli

Colovati

Moysés-Oliveira

et al. 2019

Molec Gen & Gen Med

View full text Add to dashboard Cite

BackgroundOculo‐auriculo‐vertebral spectrum (OAVS) is a craniofacial developmental disorder that affects structures derived from the first and second pharyngeal arches. The clinically heterogeneous phenotype involves mandibular, oral, and ear development anomalies. Etiology is complex and poorly understood. Genetic factors have been associated, evidenced by chromosomal abnormalities affecting different genomic regions and genes. However, known pathogenic single‐nucleotide variants (SNVs) have only been identified in MYT1 in a restricted number of patients. Therefore, investigations of SNVs on candidate genes may reveal other pathogenic mechanisms. MethodsIn a cohort of 73 patients, coding and untranslated regions (UTR) of 10 candidate genes (CRKL, YPEL1, MAPK1, NKX3‐2, HMX1, MYT1, OTX2, GSC, PUF60, HOXA2) were sequenced. Rare SNVs were selected and in silico predictions were performed to ascertain pathogenicity. Likely pathogenic variants were validated by Sanger sequencing and heritability was assessed when possible.ResultsFour likely pathogenic variants in heterozygous state were identified in different patients. Two SNVs were located in the 5’UTR of YPEL1; one in the 3’UTR of CRKL and one in the 3’UTR of OTX2.ConclusionOur work described variants in candidate genes for OAVS and supported the genetic heterogeneity of the spectrum.

show abstract

Section: Discussionmentioning

confidence: 62%

Rare single‐nucleotide variants in oculo‐auriculo‐vertebral spectrum (OAVS)

Zamariolli

Colovati

Moysés-Oliveira

et al. 2019

Molec Gen & Gen Med

View full text Add to dashboard Cite

show abstract

“…OTX2 regulates various transcription factors including RX1, PAX6, SIX3, LHX2, MITF, GBX2, and HESX1 in order to coordinate cell determination and differentiation. In humans, 21 heterozygous de novo OTX2 mutations and one microdeletion [41] have been reported [42][43][44][45] in patients with structural eye malformations (microphthalmia, anophthalmia, underdeveloped left optic nerve, ocular coloboma) and congenital hypopituitarism. Patients present with variable hypopituitarism [46][47][48] with GH-the most vulnerable pituitary hormone-deficiency and variable brain abnormalities (MRI findings range from normal or hypoplastic anterior pituitary, normal or ectopic posterior pituitary and Chiari malformation).…”

Section: Septo-optic Dysplasia and Other Eye Abnormalitiesmentioning

confidence: 99%

Congenital Hypopituitarism: Various Genes, Various Phenotypes

et al. 2019

View full text Add to dashboard Cite

The ontogenesis and development of the pituitary gland is a highly complex process that depends on a cascade of transcription factors and signaling molecules. Spontaneous mutations and transgenic murine models have demonstrated a role for many of these factors, including HESX1, PROP1, PIT1, LHX3, LHX4, SOX2, SOX3, OTX2, PAX6, FGFR1, SHH, GLI2, and FGF8 in the etiology of congenital hypopituitarism. Genetic mutations in any of these factors can lead to congenital hypopituitarism, which is characterized by the deficiency in one or more pituitary hormones. The phenotype can be highly variable, consisting of isolated hypopituitarism or more complex disorders. The same phenotype can be attributed to different gene mutations; while a given gene mutation can induce different phenotypes. This review highlights the genetic variations that lead to congenital hypopituitarism and their associated defects. The overall incidence of mutations in known transcription factors in patients with hypopituitarism is low; therefore many gene mutations or even gene- epigenetic interactions have to be unraveled in the future to explain the vast majority of still unclear cases of congenital hypopituitarism.

show abstract

“…The combination of structural abnormalities in separate organ systems increased the likelihood of an underlying genetic etiology with the association of intellectual disability. Bilateral microphthalmia has also been associated with pituitary abnormalities and consequent endocrine dysfunction in some cases (Jones et al, ). The couple requested a termination of pregnancy and the female baby was born at 21 weeks of gestation weighing 420g (50th centile) and measuring 25cm crown‐heel length (17th centile).…”

Section: Clinical Reportmentioning

confidence: 99%

Fetal diagnosis of Mowat‐Wilson syndrome by whole exome sequencing

Evans

Pinner

Chan

et al. 2019

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Mowat-Wilson syndrome (MWS) is a complex genetic disorder associated with heterozygous variation in ZEB2. It is mainly characterized by moderate-to-severe intellectual disability, facial dysmorphism, epilepsy, and various malformations including Hirschsprung disease, corpus callosum anomalies, and congenital heart defects. It is rarely diagnosed prenatally and there is limited information available on the prenatal phenotype associated with MWS. Here we report the detection of a heterozygous de novo nonsense variant in ZEB2 by whole exome sequencing in a fetus with microphthalmia in addition to cardiac defects and typical MWS facial dysmorphism. As the prenatal phenotypic spectrum of MWS expands, the routine addition of fetal genomic testing particularly in the presence of multiple malformations will increase both the sensitivity and specificity of prenatal diagnostics. K E Y W O R D Sfetus, genomic testing, prenatal diagnosis, ZEB2, Mowat-Wilson syndrome

show abstract

14q22.3 Microdeletion encompassing OTX2 in a five-generation family with microphthalmia, pituitary abnormalities, and intellectual disability

Cited by 5 publications

References 6 publications

Rare single‐nucleotide variants in oculo‐auriculo‐vertebral spectrum (OAVS)

Rare single‐nucleotide variants in oculo‐auriculo‐vertebral spectrum (OAVS)

Congenital Hypopituitarism: Various Genes, Various Phenotypes

Fetal diagnosis of Mowat‐Wilson syndrome by whole exome sequencing

Contact Info

Product

Resources

About