Health indicators

[fred_herbert]

I read a study (I can't be bothered to find it now, but it is there) where they analyzed the different health indicators and concluded that they are extremely important for attractiveness. And I agree completely. The things that they mentioned were:

skin color / tan - very pale skin (even on an ethnic) is a death sentence, it's a sign of a reclusive lifestyle and just looks unhealthy, I rarely see pale guys with girlfriends.

skin - issues such as: acne, eczema, dandruff, eye circles, etc - this is just a sign of a shit immune system, illness or diet and women HATE IT

hair - thin and / or balding hair is another death sentence, again it just looks unhealthy

body fat - probably the biggest looks killer of them all, its one of the most realiable indicators of an unhealthy lifestyle and therefore one of the most unattractive traits in this list.

muscle mass - not as important, but having extremely low levels of muscle mass is a big problem

I don't believe that having all of these in check is enough to ascend as an incel. However the majority of incels have one or more of these problems. I RARELY see men who several of those issues with girlfriends. I consider them more as a requirement that you need to meet before a girl would consider you. So if you have potential and you have those issues, fixing them could be a game changer. And remember no matter how chad your face and frame is, if you have pale deathly skin, balding hair, acne, eye circles, etc you will be incel.

 

[Gremlincel]

I'm not human.

 

[youngswedecel]

LMAO LOW IQ POST

I have fucking none of these issues and I am still KHHHV

 

[Gremlincel]

LMAO LOW IQ POST

I have fucking none of these issues and I am still KHHHV

"Anything I don't have must be attractive"

 

[youngswedecel]

"Anything I don't have must be attractive"

Same with the fucking heightcopers, as long as you aren't under 5"7 height doesnt matter smh. Face gives you slaying powers, height gives you mogging powers

 

[Gremlincel]

Same with the fucking heightcopers, as long as you aren't under 5"7 height doesnt matter smh. Face gives you slaying powers, height gives you mogging powers

No, I meant, you claimed that, since you had none of these issues and were still incel, that it was a low IQ post, when that isn't the case. OP is right, and if you had all of these issues your SMV would absolutely be far, far lower.

 

[Ritalincel]

cope

 

[fred_herbert]

LMAO LOW IQ POST

I have fucking none of these issues and I am still KHHHV

Can you even read?

I don't believe that having all of these in check is enough to ascend as an incel.

As I already said in the initial post, fixing those issues can help if you are an incel with potential, aka ur not ugly, not manlet, etc.

 

[caudino]

as long as you aren't under 5"7 height doesnt matter smh

I'm short and in my experience height matters a lot. I would agree if you said 'under 6'. But 5"7...? That's not enough, not even close

 

[Intellau_Celistic]

Alright. We'll begin by reviewing the genetic data.

The proband is...an incel.

Patient Medical History:

Surgery performed on a different occasion:

 

[Intellau_Celistic]

Disregarding interlopers, we'll review the genetic data now:

We briefly note the population frequency:

1000Genomes_30x	Global	Study-wide	6404	T=0.9998	G=0.0002
1000Genomes_30x	African	Sub	1786	T=0.9994	G=0.0006
1000Genomes_30x	Europe	Sub	1266	T=1.0000	G=0.0000
1000Genomes_30x	South Asian	Sub	1202	T=1.0000	G=0.0000
1000Genomes_30x	East Asian	Sub	1170	T=1.0000	G=0.0000
1000Genomes_30x	American	Sub	980	T=1.000	G=0.000

Again:

1000Genomes_30x	Global	Study-wide	6404	C=0.9922	T=0.0078
1000Genomes_30x	African	Sub	1786	C=0.9720	T=0.0280
1000Genomes_30x	Europe	Sub	1266	C=1.0000	T=0.0000
1000Genomes_30x	South Asian	Sub	1202	C=1.0000	T=0.0000
1000Genomes_30x	East Asian	Sub	1170	C=1.0000	T=0.0000
1000Genomes_30x	American	Sub	980	C=1.000	T=0.000

Very rare variants indeed.

We corroborate this with an SNP analysis:

...

 

[Agent47]

 

[Intellau_Celistic]

We'll proceed to the data available for known variants:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477736/

Background​

Greig cephalopolysyndactyly syndrome is a rare multiple congenital anomaly syndrome characterized by the triad of polysyndactyly (preaxial or mixed preaxial and postaxial), macrocephaly, and ocular hypertelorism. Little is known about the neuropsychological phenotype and the developmental features of this syndrome.

Case presentation​

We describe the clinical features of a 7-year-old Italian white boy affected by Greig cephalopolysyndactyly syndrome in comorbidity with autism spectrum disorder and the case of his 45-year-old white father, carrying the same point deletion (c.3677del) in the GLI3 gene and showing subclinical autistic symptoms. We performed a neuropsychiatric assessment of cognitive, adaptive, socio-communicative, and behavioral skills of the child. Concurrently, the father underwent his first psychiatric evaluation of cognitive skills and autistic symptoms.

We report the first clinical description of an association between autistic symptoms and Greig cephalopolysyndactyly syndrome in two members of the same family with the same genetic point deletion. Further research is required in order to draw an accurate conclusion regarding the association between Greig cephalopolysyndactyly syndrome and autism.
Keywords: Greig cephalopolysyndactyly syndrome, Autism, Neuropsychological phenotype, Development, Intellectual disability, Comorbidity

A 7-year-old Italian white boy affected by GCPS and ASD was referred to our Child Psychiatry Unit for a neuropsychiatric assessment.

The child, born of non-consanguineous white parents, was born at 40 weeks of gestation by vaginal delivery. A previous spontaneous miscarriage was reported. His birth weight was 3070 g (15–50th centile), length 49 cm (15–50th centile), head circumference 34 cm (15–50th centile), and APGAR Index 9–10. He was born with postaxial polysyndactyly of his hands (right hand had two extra fingers, partial syndactyly of finger 5–6; left hand had one extra finger) and of his right foot (one extra toe), surgically corrected at 6 months of age. In the early perinatal period, due to the observed dysmorphic features, the child underwent brain ultrasound (referred as normal) and genetic counseling without specific indication for subsequent genetic screening.

The diagnosis of GCPS was clinically suspected in both the child and his father respectively at 3 and 42 years of age, and later molecularly confirmed through direct sequencing and multiplex ligation-dependent probe amplification (MLPA): “heterozygous for the single nucleotide deletion c.3677del, point mutation paternally transmitted, not previously described, localized in gene’s region associated with GCPS, resulting in a truncated GLI3 protein caused by the frameshift mutation and the insertion of a premature stop codon (Pro1226Glnfs4)” (see Fig. 1 for the chromatogram).

On our clinical examination at 7 years and 5 months of age, he weighed 26 kg (50–85th centile), his height was 126 cm (50–85th centile), and his head circumference around was 54.3 cm (98th centile); frontal bossing, a prominent forehead, hypertelorism, a flat nasal bridge, and low-set ears were present. A neurological examination showed normal cranial nerves, and regular muscular tropism and tone. No sensory or autonomic involvement was observed. Deep tendon reflexes of superior and lower limbs were present and normal. The Finger-to-Nose test, performed with open eyes, due to lack of collaboration, showed mild hesitation. A widespread ligament lassitude and a mild deficiency of superior limbs’ strength were observed.

We performed a neuropsychiatric assessment of cognitive, adaptive, socio-communicative, and behavioral skills through standardized tools (see Table 1); in detail, the Leiter International Performance Scale, Third Edition (Leiter-3) [10] and the Coloured Progressive Matrices (CPM) [11] were administered revealing a non-verbal intellectual quotient (IQ) of 71 and inclusion between 10 and 25th centile (range 75–85).

...

The father’s clinical and molecular diagnosis of GCPS was made together with his son’s genetic consultation. Both carried the same single nucleotide deletion in the GLI3 gene (c.3677del). Until 42 years of age he underwent no genetic examination.

He was born of Italian non-consanguineous white parents with postaxial polydactyly of the hands and of the right foot and congenital clubfoot, which were surgically operated on after birth. No genetic counseling and screening were performed in the perinatal and postnatal period. Developmental milestones were referred as normal. No academic difficulties were reported and he graduated with success. No family history of neuropsychiatric diseases emerged.

Concurrently with the child’s evaluation, we performed a neuropsychological assessment of the 45-year-old father. Until our clinical examination, he had never undergone a psychiatric evaluation. In particular, a cognitive assessment and a specific evaluation of autistic symptoms were performed (see Table 2). His non-verbal IQ, measured by Standard Progressive Matrices (SPM) [16], turned out to be above average (IQ 128). Autistic symptoms were measured with the ADOS-2 [13]. We performed Module 4, which is suitable for adults with fluent speech. The diagnostic algorithm was composed of two main domains: Communication domain (C domain) and Social Relationship domain (SR domain); the algorithm revealed a total score of 5 (C domain 2 + SR domain 3) which does not exceed the general cut-off for the “spectrum” (7) or for “autism” (10). The partial score of the C domain, however, reached the cut-off for the “spectrum” (2).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477736/

...

 

[Intellau_Celistic]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC15863/

The phenotypic spectrum of GLI3 mutations includes autosomal dominant Greig cephalopolysyndactyly syndrome (GCPS) and Pallister–Hall syndrome (PHS). PHS was first described as a lethal condition associating hypothalamic hamartoma, postaxial or central polydactyly, anal atresia and bifid epiglottis. Typical GCPS combines polysyndactyly of hands and feet and craniofacial features. Genotype–phenotype correlations have been found both for the location and the nature of GLI3 mutations, highlighting the bifunctional nature of GLI3 during development. Here we report on the molecular and clinical study of 76 cases from 55 families with either a GLI3 mutation (49 GCPS and 21 PHS), or a large deletion encompassing the GLI3 gene (6 GCPS cases). Most of mutations are novel and consistent with the previously reported genotype–phenotype correlation. Our results also show a correlation between the location of the mutation and abnormal corpus callosum observed in some patients with GCPS. Fetal PHS observations emphasize on the possible lethality of GLI3 mutations and extend the phenotypic spectrum of malformations such as agnathia and reductional limbs defects. GLI3 expression studied by in situ hybridization during human development confirms its early expression in target tissues.

New insights into genotype–phenotype correlation for GLI3 mutations - European Journal of Human Genetics

The phenotypic spectrum of GLI3 mutations includes autosomal dominant Greig cephalopolysyndactyly syndrome (GCPS) and Pallister–Hall syndrome (PHS). PHS was first described as a lethal condition associating hypothalamic hamartoma, postaxial or central polydactyly, anal atresia and bifid...

www.nature.com

The study of patients with rare multiple congenital anomaly syndromes can provide illuminating insights into normal development and the pathogenesis of congenital anomalies. The GLI3 gene is a particularly good example as it illuminates the phenomena of pleiotropy, phenocopies, syndrome families, and evolutionary conservation of pathogenesis, and raises questions about how diagnoses are conceptualised. These topics are reviewed in turn, in the context of the clinical and biological data derived from patients with mutations in GLI3 and experimental work in model systems.

What you can learn from one gene: GLI3 | Journal of Medical Genetics

Greig cephalopolysyndactyly syndrome (GCPS) and isolated preaxial polydactyly type IV (PPD-IV) are rare autosomal dominant disorders, both caused by mutations in the GLI3 gene. GCPS is mainly characterised by craniofacial abnormalities (macrocephaly/prominent forehead, hypertelorism) and limb malformations, such as PPD-IV, syndactyly and postaxial polydactyly type A or B (PAPA/B). Mutations in the GLI3 gene can also lead to Pallister–Hall syndrome (PHS) and isolated PAPA/B. In this study, we investigated 16 unrelated probands with the clinical diagnosis of GCPS/PPD-IV and found GLI3 mutations in 12 (75 %) of them (nine familial and three sporadic cases). We also performed a detailed clinical evaluation of all 12 GLI3-positive families, with a total of 27 patients. The hallmark triad of GCPS (preaxial polydactyly, macrocephaly/prominent forehead, hypertelorism) was present in 14 cases (52 %), whereas at least one typical dysmorphic feature was manifested in 17 patients (63 %). Upon sequencing of the GLI3 gene, we demonstrated eight novel and two previously reported heterozygous point mutations. We also performed multiplex ligation-dependent probe amplification (MLPA) to screen for intragenic copy number changes and identified heterozygous deletions in the two remaining cases (16.7 %). Our findings fully support previous genotype–phenotype correlations, showing that exonic deletions, missense mutations, as well as truncating variants localised out of the middle third of the GLI3 gene result in GCPS/PPD-IV and not PHS. Additionally, our study shows that intragenic GLI3 deletions may account for a significant proportion of GCPS/PPD-IV causative mutations. Therefore, we propose that MLPA or quantitative polymerase chain reaction (qPCR) should be implemented into routine molecular diagnostic of the GLI3 gene.

Expanded mutational spectrum of the GLI3 gene substantiates genotype–phenotype correlations - Journal of Applied Genetics

Greig cephalopolysyndactyly syndrome (GCPS) and isolated preaxial polydactyly type IV (PPD-IV) are rare autosomal dominant disorders, both caused by mutations in the GLI3 gene. GCPS is mainly characterised by craniofacial abnormalities (macrocephaly/prominent forehead, hypertelorism) and limb...

link.springer.com

It's not something that can be refuted.

 

[Intellau_Celistic]

There is SSD, of-course, though this really isn't the thread for that:

PPI deficits are thought to reflect abnormalities in processing and integration of sensory and motor information. Two prior studies found that OCD patients had PPI deficits at single prepulse (PP) intensities. However, most patients in these studies were taking psychotropic medications at the time of PPI testing, and preclinical studies have demonstrated effects of psychotropic medications on PPI. We examined PPI in 22 unmedicated OCD patients and 22 matched healthy controls at three different PP intensities (74, 78, and 86 dB). OCD patients had significantly less PPI across all three PP intensities compared with controls. Exploratory analyses indicated that OCD patients with a history of tics had lower levels of PPI. Our results demonstrate that unmedicated OCD patients have impaired sensorimotor gating as measured by PPI. This indicates that PPI deficits are present in OCD patients and are not the result of medication effects. Our findings also suggest that OCD patients with a history of tics may have greater impairment in sensorimotor gating than the general OCD population. Future studies should be designed to examine whether PPI deficits characterize tic-related OCD.

Impaired Sensorimotor Gating in Unmedicated Adults with Obsessive–Compulsive Disorder - Neuropsychopharmacology

Functional and structural imaging studies suggest that obsessive–compulsive disorder (OCD) symptoms arise from dysfunction in cortico-striato-thalamo-cortical circuits. It has therefore been hypothesized that neurophysiological tasks subserved by these circuits should be abnormal in OCD...

www.nature.com

I don't suggest anger...bias is pointless in this situation.

 

[Intellau_Celistic]

Can you even read?

I think her angle is...she dislikes the data and variants gathered, so slandering incels is the best objective.

 

[Intellau_Celistic]

...

Articles.

 

[Intellau_Celistic]

Greig cephalopolysyndactyly syndrome (GCPS, MIM#175700) and isolated preaxial polydactyly type IV (PPD-IV, MIM#174700) are rare autosomal dominant disorders, both caused by mutations in the GLI3 zinc-finger transcription factor gene (Vortkamp et al. 1991). GCPS is predominantly characterised by craniofacial abnormalities, such as macrocephaly, prominent forehead/frontal bossing, hypertelorism and limb malformation, referred to as PPD-IV, comprising duplicated halluces, with syndactyly of preaxial toes, broad or duplicated thumbs, and syndactyly of the third and fourth fingers. Additionally, postaxial polydactyly type A or B (PAPA/B) may also occur (Temtamy and McKusick 1978). Isolated PPD-IV is often included into the GCPS spectrum, as a subtype in which craniofacial dysmorphic features are mild and indistinguishable from the normal individual (Baraitser et al. 1983). Mutations in the GLI3 gene can also lead to Pallister–Hall syndrome (PHS) and occasionally to isolated PAPA/B (Kang et al. 1997; Radhakrishna et al. 1997, 1999). Clinical diagnostic criteria for GCPS vary among the studies. Biesceker (2008) proposed a combination of preaxial polydactyly or abnormally broad hallux or thumb in at least one limb, accompanied with syndactyly, macrocephaly and hypertelorism. Since such a full-blown phenotype does not occur in all patients, more relaxed criteria comprising preaxial polydactyly and at least one feature out of syndactyly, macrocephaly and hypertelorism were suggested by Johnston et al. (2005). Characteristic features typical of PHS include the presence of hypothalamic hamartoma, insertional polydactyly and bifid epiglottis (Biesecker 2008).

Expanded mutational spectrum of the GLI3 gene substantiates genotype–phenotype correlations - Journal of Applied Genetics

Greig cephalopolysyndactyly syndrome (GCPS) and isolated preaxial polydactyly type IV (PPD-IV) are rare autosomal dominant disorders, both caused by mutations in the GLI3 gene. GCPS is mainly characterised by craniofacial abnormalities (macrocephaly/prominent forehead, hypertelorism) and limb...

link.springer.com

 

[Intellau_Celistic]

Proband Source(Patent Foramen Ovale):

...

https://www.researchgate.net/publication/359627167_De_Novo_GLI3_Pathogenic_Variants_May_Cause_Hypotonia_and_a_Range_of_Brain_Malformations_Without_Skeletal_Abnormalities

...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842497/

The patient was a 2-year-old boy who underwent surgery in the Department of Orthopaedics, Tianjin Paediatric Hospital. The right hand and left foot of the patient were labelled as PAP B, and there was cutaneous webbing between the 3rd and 4th fingers of the left hand. Phenotypic variability among the other 4 affected related individuals (great-grandmother, granduncle, grandfather, and father) was evident. Their hands were diagnosed as PAP B. The affected individuals did not have craniofacial dysmorphism (Fig. 1). A novel autosomal dominant heterozygous GLI3 variant, NC_000007.14(NM_000168.5):c.1622C > T; p.(Thr541Met), located in exon 11, was identified by Sanger sequencing of the patient’s gDNA sample. His father and grandfather are heterozygous for the mutation, and his great-grandmother has passed away (Fig. 2; Table 1). This variant was predicted to be most likely damaging, with a score of 1 (sensitivity: 0; specificity: 1) by Polyphen 2 [4]. Moreover, it is forecast to affect protein function, with a score of 0.00 according to SIFT [5]. The GLI3 variant is highly conserved in the evolution of various species, suggesting the functional importance of this protein (Fig. 3). The simplified model illustrating the mutation in GLI3 located near the second zinc finger structure in the ZFD was constructed with HOPE (Fig. 4).

A novel missense variant in the GLI3 zinc finger domain in a family with digital anomalies - PubMed

Mutations in GLI3, which encodes a transcription factor of the Hedgehog signaling pathway, cause several developmental anomalies linked to inappropriate tissue patterning. Here, we report a novel missense variant in the fifth zinc finger domain of GLI3 (c.1826G>A; p.(Cys609Tyr)) initially identif …

pubmed.ncbi.nlm.nih.gov

Mutations in GLI3, which encodes a transcription factor of the Hedgehog signaling pathway, cause several developmental anomalies linked to inappropriate tissue patterning. Here, we report a novel missense variant in the fifth zinc finger domain of GLI3 (c.1826G>A; p.(Cys609Tyr)) initially identified in a proband with preaxial polydactyly type IV, developmental delay, sensorineural hearing loss, skeletal, and genitourinary anomalies. Additional family members exhibited various digital anomalies such as preaxial polydactyly, syndactyly, and postaxial polydactyly either in isolation or combined. Functional studies of Cys609Tyr GLI3 in cultured cells showed abnormal GLI3 processing leading to decreased GLI3 repressor production, increased basal transcriptional activity, and submaximal GLI reporter activity with Hedgehog pathway activation, thus demonstrating an intriguing molecular mechanism for this GLI3-related phenotype. Given the complexity of GLI3 post-translational processing and opposing biological functions as a transcriptional activator and repressor, our findings highlight the importance of performing functional studies of presumed GLI3 variants. This family also demonstrates how GLI3 variants are variably expressed.

 

[Intellau_Celistic]

Abstract​

Acrocallosal syndrome (ACS) is characterised by postaxial polydactyly, hallux duplication, macrocephaly, and absence of the corpus callosum, usually with severe developmental delay. The condition overlaps with Greig cephalopolysyndactyly syndrome (GCPS), an autosomal dominant disorder that results from mutations in the GLI3 gene. Here we report a child with agenesis of the corpus callosum and severe retardation, both cardinal features of ACS and rare in GCPS, who has a mutation in GLI3.

Since others have excluded GLI3 in ACS, we suggest that ACS may represent a heterogeneous group of disorders that, in some cases, may result from a mutation in GLI3 and represent a severe, allelic form of GCPS. The finding is important for counselling families with suspected ACS.

De novo GLI3 mutation in acrocallosal syndrome: broadening the phenotypic spectrum of GLI3 defects and overlap with murine models | Journal of Medical Genetics

 

[Intellau_Celistic]

One more from the incel proband:

An insertion in GLI2.

Very possibly associated with GLI, though we won't do that right now.

One final post.

 

[Intellau_Celistic]

Our proband has had a lifelong tremor disorder, and we doubt it is from GLI variants.

We first review previous history:

A Neurological Disease Caused By an Expanded CAG Trinucleotide Repeat in The TATA-Binding Protein Gene: A New Polyglutamine Disease?

Abstract. To investigate whether the expansion of CAG repeats of the TATA-binding protein (TBP) gene is involved in the pathogenesis of neurodegenerative diseas

academic.oup.com

https://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(99)01527-3

TBP: