Expanding the phenotypic spectrum of cardiospondylocarpofacial syndrome: From a detailed clinical and radiological observation of a boy with a novel missense variant in MAP3K7

2021 ◽  
Author(s):  
Mari Minatogawa ◽  
Noriko Miyake ◽  
Yoshinori Tsukahara ◽  
Yuko Tanabe ◽  
Takamichi Uchiyama ◽  
...  
Keyword(s):  
Missense Variant ◽  
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 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 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.

Expanding Phenotypic Spectrum of Cerebral Aspartate–Glutamate Carrier Isoform 1 (AGC1) Deficiency

2019 ◽  
Vol 51 (02) ◽  
pp. 160-163 ◽  
Author(s):  
Brian Pfeiffer ◽  
Kuntal Sen ◽  
Shagun Kaur ◽  
Kara Pappas
Keyword(s):  
Ketogenic Diet ◽  
Intractable Epilepsy ◽  
Cerebral Atrophy ◽  
Missense Variant ◽  
Psychomotor Delay ◽  
The Third ◽  
Developmental Arrest ◽  
Phenotypic Spectrum ◽  
Whole Exome ◽  
Aspartate Glutamate Carrier

Abstract Case We are reporting the third unrelated case of cerebral aspartate–glutamate carrier isoform 1 (AGC1) deficiency. Patient is a 21-month-old Yemeni male who presented with refractory seizure disorder and developmental arrest. Neuroimaging showed cerebral volume loss and diminished N-acetylaspartate (NAA) peak. Whole exome sequencing revealed a homozygous novel missense variant in the SLC25A12 gene. Patient's seizure frequency abated drastically following initiation of ketogenic diet. Discussion and Conclusion Cerebral AGC1 deficiency results in dysfunction of mitochondrial malate aspartate shuttle, thereby prohibiting myelin synthesis. There are significant phenotypic commonalities between our patient and previously reported cases including intractable epilepsy, psychomotor delay, cerebral atrophy, and diminished NAA peak. Our report also provides evidence regarding beneficial effect of ketogenic diet in this rare neurometabolic epilepsy.

scholarly journals Expanding the phenotypic spectrum of GABRG2 variants: a recurrent GABRG2 missense variant associated with a severe phenotype

2017 ◽  
Vol 31 (1-2) ◽  
pp. 30-36 ◽  
Author(s):  
Fanggeng Zou ◽  
Kirsty McWalter ◽  
Lindsay Schmidt ◽  
Amy Decker ◽  
Jonathan D. Picker ◽  
...  
Keyword(s):  
Missense Variant ◽  
Severe Phenotype ◽  
Phenotypic Spectrum

Alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism: Phenotypic spectrum of ATP1A3-associated disorders

2013 ◽  
Vol 44 (02) ◽  
Author(s):  
K Brockmann ◽  
H Rosewich ◽  
H Thiele ◽  
U Maschke ◽  
P Huppke ◽  
...  
Keyword(s):  
Rapid Onset ◽  
Alternating Hemiplegia Of Childhood ◽  
Phenotypic Spectrum
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