Identification of a novel variant in GPR56/ADGRG1 gene through whole exome sequencing in a consanguineous Pakistani family

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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Whole exome sequencing identified two novel homozygous missense variants in the same codon of CLCN7 underlying autosomal recessive infantile malignant osteopetrosis in a Pakistani family

Molecular Biology Reports ◽

10.1007/s11033-018-4194-8 ◽

2018 ◽

Vol 45 (4) ◽

pp. 565-570 ◽

Cited By ~ 1

Author(s):

Muhammad Aman Khan ◽

Aman Ullah ◽

Muhammad Naeem

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Autosomal Recessive ◽

Pakistani Family ◽

Missense Variants ◽

Whole Exome ◽

Malignant Osteopetrosis ◽

Infantile Malignant Osteopetrosis

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Whole-exome sequencing in a consanguineous Pakistani family identifies a mutational hotspot in the COL7A1 gene, causing recessive dystrophic epidermolysis bullosa

Clinical Dysmorphology ◽

10.1097/mcd.0000000000000299 ◽

2020 ◽

Vol 29 (2) ◽

pp. 86-89

Author(s):

Atta Ur Rehman ◽

Virginie G. Peter ◽

Mathieu Quinodoz ◽

Muhammad Dawood ◽

Carlo Rivolta

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Epidermolysis Bullosa ◽

Pakistani Family ◽

Dystrophic Epidermolysis Bullosa ◽

Whole Exome ◽

Recessive Dystrophic Epidermolysis Bullosa ◽

Col7a1 Gene

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A Novel Missense Variant of TP63 Heterozygously Present in Split-Hand/Foot Malformation

BioMed Research International ◽

10.1155/2020/4215632 ◽

2020 ◽

Vol 2020 ◽

pp. 1-5

Author(s):

Hao Geng ◽

Dongdong Tang ◽

Chuan Xu ◽

Xiaojin He ◽

Zhiguo Zhang

Keyword(s):

Blood Sample ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Peripheral Blood ◽

Sanger Sequencing ◽

Missense Variant ◽

Chinese Family ◽

Peripheral Blood Sample ◽

Whole Exome ◽

Novel Variant

Background. Split-hand/foot malformation (SHFM) is a severe congenital disability mainly characterized by the absence or hypoplasia of the central ray of the hand/foot. To date, several candidate genes associated with SHFM have been identified, including TP63, DLX5, DLX6, FGFR1, and WNT10B. Herein, we report a novel variant of TP63 heterozygously present in affected members of a family with SHFM. Methods. This study investigated a Chinese family, in which the proband and his son suffered from SHFM. The peripheral blood sample of the proband was used to perform whole-exome sequencing (WES) to explore the possible genetic causes of this disease. Postsequencing bioinformatic analyses and Sanger sequencing were conducted to verify the identified variants and parental origins on all family members in the pedigree. Results. By postsequencing bioinformatic analyses and Sanger sequencing, we identified a novel missense variant (NM_003722.4:c.948G>A; p.Met316Ile) of TP63 in this family that results in a substitution of methionine with isoleucine, which is probably associated with the occurrence of SHFM. Conclusion. A novel missense variant (NM_003722.4:c.948G>A; p.Met316Ile) of TP63 in SHFM was thus identified, which may enlarge the spectrum of known TP63 variants and also provide new approaches for genetic counselling of families with SHFM.

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276 A new face for an old foe?

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-abn.140 ◽

2018 ◽

Vol 89 (10) ◽

pp. A40.3-A40 ◽

Cited By ~ 1

Author(s):

Sangha Gavinda ◽

Bron Anthony ◽

Donaghy Michael ◽

Evans Cerys ◽

Hardcastle Alison ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Family Members ◽

Calcium Sensitivity ◽

Actin Binding ◽

Cranial Neuropathy ◽

Limb Weakness ◽

Proteolytic Cascade ◽

Whole Exome ◽

Novel Variant

BackgroundMutations in the protein gelsolin result in hereditary systemic amyloidosis, characterised by onset of corneal lattice dystrophy in the third decade, a slowly progressive cranial neuropathy and cutis laxa. To date four dominantly inherited gelsolin mutations have been identified, two mutations resulting in the classical syndrome and two mutations resulting in renal-predominant amyloidosis.MethodsWe identified a family in which four individuals in three generations presented with corneal lattice dystrophy and neurological symptoms. Detailed clinical neurological and ophthalmological assessment and investigations including neurophysiology and imaging were performed. Whole exome sequencing was undertaken in three family members.ResultsWhole exome sequencing revealed a novel variant in the gelsolin gene (c. G1738A; p. E580K), dominantly inherited and predicted to be pathogenic. Examination, neurophysiological testing and imaging revealed the presence of distal upper limb weakness and wasting, corneal lattice dystrophy and cervical myelopathy in all affected family members.ConclusionThe E580K mutation described in this family is in a conserved calcium-sensitive actin-binding domain that displays sequence homology with other actin-depolymerising proteins. Mutations in this domain may result in abnormal gelsolin-actin interactions and changes in calcium sensitivity may render the protein susceptible to the same aberrant proteolytic cascade as with other known mutations.

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