Novel Missense Variant in Heterozygous State in the BRPF1 Gene Leading to Intellectual Developmental Disorder With Dysmorphic Facies and Ptosis

Naseer, Muhammad Imran; Abdulkareem, Angham Abdulrahman; Guzmán‐Vega, Francisco J.; Arold, Stefan T.; Pushparaj, Peter Natesan; Chaudhary, Adeel G.; Al-Qahtani, Mohammad H.

doi:10.3389/fgene.2020.00368

Cited by 14 publications

(21 citation statements)

References 14 publications

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“…In the last 2 years, 20 new cases were reported with BRPF1 gene variants (Demeulenaere et al, 2019; Keywan et al, 2020; Naseer et al, 2020; Yan et al, 2020). This could reflect an undiagnosed disorder within the group of patients with ID and dysmorphic features.…”

Section: Discussionmentioning

confidence: 99%

“…Besides ID, one of the most prominent signs were eyelids ptosis and blepharophimosis. Other ocular findings were downslanted palpebral fissures, optic nerve hypoplasia, nystagmus, strabismus, and amblyopia (Mattioli et al, 2017;Naseer et al, 2020;Pode-Shakked et al, 2019;Yan et al, 2020). One patient was reported with bilateral iris coloboma and facial palsy (Demeulenaere et al, 2019) Considering the importance of BRPF1 gene in molecular regulation, we can hypothesize that it can also affect all types of cells and affects the gene expression modification even in the mitochondrial metabolic pathways that are widely known to be under the control of nuclear DNA (Herai et al, 2017).…”

Section: T a B L E 1 Previous Reports Indicating Individuals With Cli...mentioning

confidence: 99%

“…They identified in the patients a heterozygous mutation in the BRPF1 gene (Bromodomain and PHD Finger Containing 1), an important transcriptional regulator responsible for histone modifications. More recently, another 20 patients were reported (Demeulenaere et al, 2019; Keywan et al, 2020; Naseer et al, 2020; Pode‐Shakked et al, 2019; Yan et al, 2020) with mutations in the same gene, suggesting that genetic variations in this gene could be a frequent cause of undiagnosed patients with intellectual disability and congenital ptosis.…”

Section: Introductionmentioning

confidence: 99%

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BRPF1‐associated syndrome: A patient with congenital ptosis, neurological findings, and normal intellectual development

Souza

Valle²,

Santos³

et al. 2022

American J of Med Genetics Pt A

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In 2017, Mattiolli et al. and Yan et al. described a series of patients with clinical findings essentially characterized by intellectual disabilities, ptosis, hypotonia, epilepsy, and weakness. They also found in these patients distinct heterozygous mutations in the BRPF1 gene, which plays a role in epigenetic regulation by promoting histone acetylation. The disease is known as Intellectual Developmental Disorder with Dysmorphic Facies and Ptosis (IDDDFP, OMIM #617333). Later, another 20 patients were also described by distinct reports, suggesting IDDDFP could be a more frequent cause of intellectual disability as it was thought before. Here, we describe a patient with normal intellectual development who had congenital ptosis, hypotonia, muscular weakness, atlanto-axial malformation, and pyramidal at the neurological examination.The patient has a rare nonsense variant on exon 3 of BRPF1 gene. We also describe a phenotypic amplification for conditions related to deficiency in histone modifications.

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Section: Discussionmentioning

confidence: 99%

Section: T a B L E 1 Previous Reports Indicating Individuals With Cli...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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BRPF1‐associated syndrome: A patient with congenital ptosis, neurological findings, and normal intellectual development

Souza

Valle²,

Santos³

et al. 2022

American J of Med Genetics Pt A

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“…Further WES results were validated with the Sanger sequencing technique using the targeted primers of the reported sequence variation in the BTD gene. Sanger sequencing was performed as previously explained by Naseer et al ( 18 ). This variation was not identified even in 100 unrelated healthy individuals in the population.…”

Section: Methodsmentioning

confidence: 99%

Whole-Exome Sequencing Reveals a Missense Variant c.1612C>T (p.Arg538Cys) in the BTD Gene Leading to Neuromyelitis Optica Spectrum Disorder in Saudi Families

et al. 2022

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Biotinidase deficiency is an autosomal recessive, multiple carboxylase deficiency usually associated with seizures, eczema, hypotonia, visual disturbances, hearing loss, and developmental delays. Only a handful of cases of biotinidase deficiency that had clinical features of neuromyelitis optica spectrum disorder have been reported in the literature. The case report study is about the clinical and genetic features of two pediatric patients from different families with biotinidase deficiency whose brain and spine MRI scans were suggestive of neuromyelitis optica. Neither child improved with immunotherapy. They come from a first-degree blood-related family. In both cases, a deficiency of the enzyme biotinidase was detected. The missense variant NM_001370658.1 (BTD):c.1612C>T (p.Arg538Cys) NM_000060.4 in exon 4 was identified by whole-exome sequencing. The identified sequence variation was validated using Sanger sequencing analysis. The intake of biotin resulted in clinical improvement. After a follow-up period of 12 months, the patient was gradually weaned from tracheostomy. His vision had improved significantly. He was able to walk and run independently. In conclusion, biotinidase deficiency is a rare and treatable cause of neuromyelitis optica. Early diagnosis can prevent poor clinical outcomes. Biotinidase enzyme levels should be considered as part of the examination algorithm for neuromyelitis optica spectrum disorder.

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“…To do the WES DNA of the affected individual was enriched for the whole coding region and splice site junctions of all the genes. The products are sequenced on an illumine NextSeq instrument with 2x76 paired end reads as previously done ( Naseer et al, 2020 ). The sequence is compared to a reference sequences GRCH37/UCSC hg19 human genome build.…”

Section: Methodsmentioning

confidence: 99%

Next generation sequencing reveals novel homozygous frameshift in PUS7 and splice acceptor variants in AASS gene leading to intellectual disability, developmental delay, dysmorphic feature and microcephaly

Naseer

Abdulkareem

Jan

et al. 2020

Saudi Journal of Biological Sciences

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Intellectual developmental disorder with abnormal behavior, microcephaly and short stature (IDDABS), (OMIM# 618342) is an autosomal recessive condition described as developmental delay, poor or absent speech, intellectual disability, short stature, mild to progressive microcephaly, delayed psychomotor development, hyperactivity, seizure, along with mild to swear aggressive behavior. Homozygous frameshift mutation in Pseudouridine Synthase 7, Putative; (PUS7) OMIM# 616,261 NM_019042.3 and splice acceptor variants in Alpha-Aminoadipic Semialdehyde Synthase; (AASS) OMIM# 605,113 NM_005763.3 was funded. Whole exome sequencing (WES) technique was used as tool to identify the molecular diagnostic test. Different bioinformatics analysis done for WES data and we identified two novel mutations one as frameshift mutation c.606_607delGA, p.Ser282CysfsTer9 in the PUS7 gene and splice acceptor variants c.1767–1 G > A in the AASS gene has been reported. The pattern of family segregation maintained the pathogenicity of this variation associated with abnormal behavior, intellectual developmental disorder, microcephaly along with short stature IDDABS. Further, the WES data was validated in the family having other affected individuals and healthy controls (n = 100) was done using Sanger sequencing. Finally, our results further explained the role of WES in the disease diagnosis and elucidated that the mutation in PUS7 and AASS genes may lead an important role for the development of IDDABS in Saudi family.

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Novel Missense Variant in Heterozygous State in the BRPF1 Gene Leading to Intellectual Developmental Disorder With Dysmorphic Facies and Ptosis

Cited by 14 publications

References 14 publications

BRPF1‐associated syndrome: A patient with congenital ptosis, neurological findings, and normal intellectual development

BRPF1‐associated syndrome: A patient with congenital ptosis, neurological findings, and normal intellectual development

Whole-Exome Sequencing Reveals a Missense Variant c.1612C>T (p.Arg538Cys) in the BTD Gene Leading to Neuromyelitis Optica Spectrum Disorder in Saudi Families

Next generation sequencing reveals novel homozygous frameshift in PUS7 and splice acceptor variants in AASS gene leading to intellectual disability, developmental delay, dysmorphic feature and microcephaly

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