SMG9 ‐deficiency syndrome caused by a homozygous missense variant: Expanding the genotypic and phenotypic spectrum of this developmental disorder

2020 ◽  
Vol 182 (7) ◽  
pp. 1829-1831 ◽  
Author(s):  
Gabrielle Lemire ◽  
Stella K. MacDonald ◽  
Kym M. Boycott
Keyword(s):  
Developmental Disorder ◽  
Missense Variant ◽  
Deficiency Syndrome ◽  
Phenotypic Spectrum

scholarly journals Allelic Variants in Established Hypopituitarism Genes Expand Our Knowledge of the Phenotypic Spectrum

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1128
Author(s):  
Marilena Nakaguma ◽  
Nathalia Garcia Bianchi Pereira Ferreira ◽  
Anna Flavia Figueredo Benedetti ◽  
Mariana Cotarelli Madi ◽  
Juliana Moreira Silva ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Male Patient ◽  
Missense Variant ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Incomplete Penetrance ◽  
Growth Hormone Gene ◽  
Posterior Lobe ◽  
Allelic Variants ◽  
Phenotypic Spectrum

We report four allelic variants (three novel) in three genes previously established as causal for hypopituitarism or related disorders. A novel homozygous variant in the growth hormone gene, GH1 c.171delT (p.Phe 57Leufs*43), was found in a male patient with severe isolated growth hormone deficiency (IGHD) born to consanguineous parents. A hemizygous SOX3 allelic variant (p.Met304Ile) was found in a male patient with IGHD and hypoplastic anterior pituitary. YASARA, a tool to evaluate protein stability, suggests that p.Met304Ile destabilizes the SOX3 protein (ΔΔG = 2.49 kcal/mol). A rare, heterozygous missense variant in the TALE homeobox protein gene, TGIF1 (c.268C>T:p.Arg90Cys) was found in a patient with combined pituitary hormone deficiency (CPHD), diabetes insipidus, and syndromic features of holoprosencephaly (HPE). This variant was previously reported in a patient with severe holoprosencephaly and shown to affect TGIF1 function. A novel heterozygous TGIF1 variant (c.82T>C:p.Ser28Pro) was identified in a patient with CPHD, pituitary aplasia and ectopic posterior lobe. Both TGIF1 variants have an autosomal dominant pattern of inheritance with incomplete penetrance. In conclusion, we have found allelic variants in three genes in hypopituitarism patients. We discuss these variants and associated patient phenotypes in relation to previously reported variants in these genes, expanding our knowledge of the phenotypic spectrum in patient populations.

TBL1XR1 associated intellectual disability, a new missense variant with dysmorphic features plus autism: Expanding the phenotypic spectrum

2021 ◽  
Author(s):  
Ignacio Arroyo Carrera ◽  
Miguel Fernández‐Burriel ◽  
Pablo Lapunzina ◽  
Jair Antonio Tenorio ◽  
Verónica Deyanira García Navas ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Missense Variant ◽  
Dysmorphic Features ◽  
Phenotypic Spectrum

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

2020 ◽  
Vol 11 ◽  
Author(s):  
Muhammad Imran Naseer ◽  
Angham Abdulrahman Abdulkareem ◽  
Francisco J. Guzmán-Vega ◽  
Stefan T. Arold ◽  
Peter Natesan Pushparaj ◽  
...  
Keyword(s):  
Developmental Disorder ◽  
Missense Variant ◽  
Heterozygous State ◽  
Intellectual Developmental Disorder

Confirmation and further delineation of the SMG9‐deficiency syndrome, a rare and severe developmental disorder

2019 ◽  
Vol 179 (11) ◽  
pp. 2257-2262
Author(s):  
François Lecoquierre ◽  
Antoine Bonnevalle ◽  
Alexandra Chadie ◽  
Claire Gayet ◽  
Clémentine Dumant‐Forest ◽  
...  
Keyword(s):  
Developmental Disorder ◽  
Deficiency Syndrome

scholarly journals Allelic Variants in Established Hypopituitarism Genes Expands Our Knowledge of Phenotypic Spectrum

2021 ◽  
Author(s):  
Marilena Nakaguma ◽  
Nathalia Garcia Bianchi Pereira Ferreira ◽  
Anna Flavia Figueredo Benedetti ◽  
Mariana Cotarelli Madi ◽  
Juliana Moreira Silva ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Male Patient ◽  
Missense Variant ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Incomplete Penetrance ◽  
Growth Hormone Gene ◽  
Posterior Lobe ◽  
Allelic Variants ◽  
Phenotypic Spectrum

We report four allelic variants (3 novel) in three genes previously established as causal for hypopituitarism or related disorders. A novel homozygous variant in the growth hormone gene, GH1 c.171delT (p. Phe 57Leufs * 43), was found in a male patient with severe isolated growth hormone deficiency (IGHD) born to consanguineous parents. A SOX3 allelic variant (p.Met304Ile) was found in a male patient with IGHD and hypoplastic anterior pituitary. YASARA, a tool to evaluate protein stability, suggests that p.Met304Ile destabilizes the SOX3 protein (ΔΔG = 2.49 kcal/mol). A rare, heterozygous missense variant in the TALE homeobox protein gene, TGIF1 (c.268C>T:p.Arg90Cys) was found in a patient with combined pituitary hormone deficiency (CPHD), diabetes insipidus, and syndromic features of holoprosencephaly (HPE). A novel heterozygous TGIF1 variant (c.82T>C:p.Ser28Pro) was identified in a patient with CPHD, pituitary aplasia and ectopic posterior lobe. Both TGIF1 variants have an autosomal dominant pattern of inheritance with incomplete penetrance. In conclusion, we have found allelic variants in 3 genes in hypopituitarism patients. We discuss these variants and associated patient phenotypes in relation to previously reported variants in these genes, expanding our knowledge of the phenotypic spectrum in patient populations.

scholarly journals Dopamine transporter deficiency syndrome: phenotypic spectrum from infancy to adulthood

Brain ◽  
2014 ◽  
Vol 137 (4) ◽  
pp. 1107-1119 ◽  
Author(s):  
Joanne Ng ◽  
Juan Zhen ◽  
Esther Meyer ◽  
Kevin Erreger ◽  
Yan Li ◽  
...  
Keyword(s):  
Dopamine Transporter ◽  
Deficiency Syndrome ◽  
Phenotypic Spectrum ◽  
Transporter Deficiency

scholarly journals Further phenotypic delineation of the auriculocondylar syndrome type 2 with literature review

2020 ◽  
Author(s):  
Ewelina Bukowska-Olech ◽  
Anna Sowińska-Seidler ◽  
Filip Łojek ◽  
Delfina Popiel ◽  
Joanna Walczak-Sztulpa ◽  
...  
Keyword(s):  
Somatic Mosaicism ◽  
Missense Variant ◽  
Pharyngeal Arches ◽  
Developmental Defects ◽  
Targeted Next Generation Sequencing ◽  
Phenotypic Spectrum ◽  
Whole Exome ◽  
Low Coverage ◽  
Generation Sequencing

AbstractAuriculocondylar syndrome (ACS) is an ultra-rare disorder that arises from developmental defects of the first and second pharyngeal arches. Three subtypes of ACS have been described so far, i.e., ACS1 (MIM: 602483), ACS2 (MIM: 600810), and ACS3 (MIM: 131240). The majority of patients, however, are affected by ACS2, which results from the mutations in the PLCB4 gene. Herein, we have described an 8-year-old male patient presenting with ACS2 and summarized the molecular and phenotypic spectrum of the syndrome. We have also compared the clinical features of our case to three other previously described cases (one sporadic and two familial) harboring the same heterozygous missense variant c.1862G>A, p.Arg621His in the PLCB4 gene. The mutation was detected using whole-exome sequencing (WES). Due to low coverage of WES and suspicion of somatic mosaicism, the variant was additionally reassessed by deep targeted next-generation sequencing panel of genes related to the craniofacial disorders, and next confirmed by Sanger sequencing. ACS2 presents high intra- and interfamilial phenotypic heterogeneity that impedes reaching an exact clinical and molecular diagnosis. Thus, describing additional cases, carrying even the known mutation, but resulting in variable phenotypes, is essential for better understanding of such orphan Mendelian diseases.

Stroke mimics add to the phenotypic spectrum of GLUT1 deficiency syndrome

2017 ◽  
Vol 89 (6) ◽  
pp. 668-670 ◽  
Author(s):  
Hilde M H Braakman ◽  
Marc Engelen ◽  
Joost Nicolai ◽  
Michèl A A P Willemsen
Keyword(s):  
Deficiency Syndrome ◽  
Stroke Mimics ◽  
Phenotypic Spectrum ◽  
Glut1 Deficiency ◽  
Glut1 Deficiency Syndrome
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