Partial gonadal dysgenesis associated with a pathogenic variant of PBX1 transcription factor

A term neonate was admitted to the Neonatal Intensive Care Unit for respiratory distress, hypotonia and atypical genitalia. Significant findings included a small phallic structure, labial folds, no palpable gonads and two perineal openings. Pelvic ultrasound showed uterine didelphys and a gonad in the right inguinal canal. The right gonad was removed during diagnostic laparoscopy with microscopic evaluation showing infantile testicular tissue and fluorescence in-situ hybridisation showed only XY signal suggesting that the removed gonad was a male-developed testis. Infant was 46,XY, SRY probe positive. The parents chose a female sex assignment prior to gonadectomy. The infant had respiratory insufficiency and central hypotonia that persisted on discharge. Whole exome sequencing showed a heterozygous pathogenic variant of the PBX1 gene. This variant encodes the pre-B-cell leukaemia homeobox PBX transcription factor and has been associated with malformations and severe hypoplasia or aplasia of multiple organs including lungs and gonads. Whole exome sequencing was crucial in providing a unifying diagnosis for this patient.

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Identification of a novel ALMS1 pathogenic variant in a family with Cone-Rod Dystrophy using whole exome sequencing, followed by prenatal diagnosis

Meta Gene ◽

10.1016/j.mgene.2018.06.006 ◽

2018 ◽

Vol 17 ◽

pp. 167-171 ◽

Cited By ~ 1

Author(s):

Maryam Rafati ◽

Seyedeh Zahra Tara ◽

Fatemeh Hoseininasab ◽

Saeed Reza Ghaffari

Keyword(s):

Prenatal Diagnosis ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Pathogenic Variant ◽

Whole Exome

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A likely pathogenic variant putatively affecting splicing ofPIGAidentified in a multiple congenital anomalies hypotonia-seizures syndrome 2 (MCAHS2) family pedigree via whole-exome sequencing

Molecular Genetics & Genomic Medicine ◽

10.1002/mgg3.428 ◽

2018 ◽

Vol 6 (5) ◽

pp. 739-748 ◽

Cited By ~ 7

Author(s):

Junli Yang ◽

Qiong Wang ◽

Qingcui Zhuo ◽

Huiling Tian ◽

Wen Li ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Congenital Anomalies ◽

Pathogenic Variant ◽

Multiple Congenital Anomalies ◽

Whole Exome ◽

Family Pedigree

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Whole exome sequencing identified a second pathogenic variant in HOMER2 for autosomal dominant non-syndromic deafness

Clinical Genetics ◽

10.1111/cge.13422 ◽

2018 ◽

Vol 94 (5) ◽

pp. 419-428 ◽

Cited By ~ 3

Author(s):

X. Lu ◽

Q. Wang ◽

H. Gu ◽

X. Zhang ◽

Y. Qi ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Autosomal Dominant ◽

Pathogenic Variant ◽

Whole Exome

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Clinical whole-exome sequencing reveals a common pathogenic variant in patients with CoQ10 deficiency: An underdiagnosed cause of mitochondriopathy

Clinica Chimica Acta ◽

10.1016/j.cca.2019.07.016 ◽

2019 ◽

Vol 497 ◽

pp. 88-94

Author(s):

Tsz-ki Ling ◽

Chun-yiu Law ◽

Kin-wing Yan ◽

Nai-chung Fong ◽

Ka-chung Wong ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Pathogenic Variant ◽

Whole Exome ◽

Coq10 Deficiency

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Novel Pathogenic Variant (c.580C>T) in the CPS1 Gene in a Newborn With Carbamoyl Phosphate Synthetase 1 Deficiency Identified by Whole Exome Sequencing

Annals of Laboratory Medicine ◽

10.3343/alm.2017.37.1.58 ◽

2017 ◽

Vol 37 (1) ◽

pp. 58-62 ◽

Cited By ~ 6

Author(s):

Rihwa Choi ◽

Hyung-Doo Park ◽

Mina Yang ◽

Chang-Seok Ki ◽

Soo-Youn Lee ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Pathogenic Variant ◽

Carbamoyl Phosphate Synthetase ◽

Carbamoyl Phosphate ◽

Whole Exome ◽

Carbamoyl Phosphate Synthetase 1

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Whole-exome sequencing identifies a novel mutation in spermine synthase gene (SMS) associated with Snyder-Robinson Syndrome

10.21203/rs.3.rs-23574/v4 ◽

2020 ◽

Author(s):

Talal J. Qazi ◽

Qiao Wu ◽

Ailikemu Aierken ◽

Daru Lu ◽

Ihtisham Bukhari ◽

...

Keyword(s):

Intellectual Disability ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Mutational Analysis ◽

Novel Mutation ◽

Pathogenic Variant ◽

Facial Dysmorphism ◽

Pakistani Family ◽

Spermine Synthase ◽

Whole Exome

Abstract Background: Loss of function mutations in the spermine synthase gene (SMS) have been reported to cause a rare X-linked intellectual disability known as Snyder-Robinson Syndrome (SRS). Besides intellectual disability, SRS is also characterized by reduced bone density, osteoporosis and facial dysmorphism. SRS phenotypes evolve with age from childhood to adulthood. Methods: Whole exome sequencing was performed to know the causative gene/pathogenic variant. Later we confirmed the pathogenic variant through Sanger sequencing. Furthermore, we also performed the mutational analysis through HOPE SERVER and SWISS-MODEL. Also, radiographs were also obtained for affected individual to confirm the disease features. Results: In this article, we report the first Pakistani family consisting of three patients with SRS and a novel missense pathogenic variant in the SMS gene (c.905 C>T p.(Ser302Leu)). In addition to the typical phenotypes, one patient presented with early-onset seizures. Clinical features, genetic and in-silico analysis linked the affected patients of the family with Snyder-Robinson and suggest that this novel mutation affects the spermine synthase activity Conclusion: A novel missense variant in the SMS, c.905C >T p. (Ser302Leu), causing Snyder- Robinson Syndrome (SRS) is reported in three members of Pakistani Family.

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Whole exome sequencing identifies a novel mutation in spermine synthase gene (SMS) associated with Snyder-Robinson Syndrome

10.21203/rs.3.rs-23574/v3 ◽

2020 ◽

Author(s):

Talal J. Qazi ◽

Qiao Wu ◽

Ailikemu Aierken ◽

Daru Lu ◽

Ihtisham Bukhari ◽

...

Keyword(s):

Intellectual Disability ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Mutational Analysis ◽

Novel Mutation ◽

Pathogenic Variant ◽

Facial Dysmorphism ◽

Pakistani Family ◽

Spermine Synthase ◽

Whole Exome

Abstract Background: Loss of function mutations in the spermine synthase gene (SMS) have been reported to cause a rare X-linked intellectual disability known as Snyder-Robinson Syndrome (SRS). Besides intellectual disability, SRS is also characterized by reduced bone density, osteoporosis and facial dysmorphism. SRS phenotypes evolve with age from childhood to adulthood. Methods: Whole exome sequencing was performed to know the causative gene/pathogenic variant. Later we confirmed the pathogenic variant through Sanger sequencing. Furthermore, we also performed the mutational analysis through HOPE SERVER and SWISS-MODEL. Also, radiographs were also obtained for affected individual to confirm the disease features. Results: In this article, we report the first Pakistani family consisting of three patients with SRS and a novel missense pathogenic variant in the SMS gene (c.905 C>T p.(Ser302Leu)). In addition to the typical phenotypes, one patient presented with early-onset seizures. Clinical features, genetic and in-silico analysis linked the affected patients of the family with Snyder-Robinson and suggest that this novel mutation affects the spermine synthase activityConclusion: A novel missense variant in the SMS, c.905C >T p. (Ser302Leu), causing Snyder- Robinson Syndrome (SRS) is reported in three members of Pakistani Family.

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Homozygous missense variant in the TTN gene causing autosomal recessive limb-girdle muscular dystrophy type 10

BMC Medical Genetics ◽

10.1186/s12881-019-0895-7 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 5

Author(s):

Amjad Khan ◽

Rongrong Wang ◽

Shirui Han ◽

Muhammad Umair ◽

Safdar Abbas ◽

...

Keyword(s):

Muscular Dystrophy ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Autosomal Recessive ◽

Missense Variant ◽

Pathogenic Variant ◽

Limb Girdle Muscular Dystrophy ◽

Molecular Diagnostic ◽

Sequencing Analysis ◽

Whole Exome

Abstract Background Limb-girdle muscular dystrophies (LGMDs) are large group of heterogeneous genetic diseases, having a hallmark feature of muscle weakness. Pathogenic mutations in the gene encoding the giant skeletal muscle protein titin (TTN) are associated with several muscle disorders, including cardiomyopathy, recessive congenital myopathies and limb-girdle muscular dystrophy (LGMD) type10. The phenotypic spectrum of titinopathies is expanding, as next generation sequencing (NGS) technology makes screening of this large gene possible. Aim This study aimed to identify the pathogenic variant in a consanguineous Pakistani family with autosomal recessive LGMD type 10. Methods DNA from peripheral blood samples were obtained, whole exome sequencing (WES) was performed and several molecular and bioinformatics analysis were conducted to identify the pathogenic variant. TTN coding and near coding regions were further amplified using PCR and sequenced via Sanger sequencing. Results Whole exome sequencing analysis revealed a novel homozygous missense variant (c.98807G > A; p.Arg32936His) in the TTN gene in the index patients. No heterozygous individuals in the family presented LGMD features. The variant p.Arg32936His leads to a substitution of the arginine amino acid at position 32,936 into histidine possibly causing LGMD type 10. Conclusion We identified a homozygous missense variant in TTN, which likely explains LGMD type 10 in this family in line with similar previously reported data. Our study concludes that WES is a successful molecular diagnostic tool to identify pathogenic variants in large genes such as TTN in highly inbred population.

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