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Ichthyosis and erythrokeratoderma v4.4 LSS Achchuthan Shanmugasundram gene: LSS was added
gene: LSS was added to Ichthyosis and erythrokeratoderma. Sources: Literature
Mode of inheritance for gene: LSS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSS were set to 30723320; 35830358
Phenotypes for gene: LSS were set to Alopecia-intellectual disability syndrome 4, OMIM:618840; alopecia-intellectual disability syndrome 4, MONDO:0030009
Review for gene: LSS was set to GREEN
Added comment: PMID:30723320 (2019) reported the identification of biallelic LSS variants in ten individuals from six unrelated families. In addition, one affected individual was identified with a single rare variant in LSS and an allelic imbalance suggesting a second event. Among the identified variants, two were truncating, seven were missense, and two were splicing variants. All 11 individuals presented with congenital alopecia and developmental delay, while ichthyosis and/ or erythroderma were found in eight of these individuals from six families.

PMID:35830358 (2022) reported a 4-day-old female patient who presented with alopecia and a previously unreported dermatologic manifestation of congenital localized hyperpigmentation. Examination of the patient also revealed features consistent with ichthyosis. The patient was identified with two variants in LSS gene and a de novo pathogenic variant in SPTAN1 gene. The SPTAN1 variant is associated with neurodevelopmental phenotypes including early infantile epileptic encephalopathy. There are no known cutaneous manifestations of SPTAN1 variant.
Sources: Literature
Ichthyosis and erythrokeratoderma v3.30 PERP Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: PERP.
Ichthyosis and erythrokeratoderma v3.30 PERP Achchuthan Shanmugasundram commented on gene: PERP: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Ichthyosis and erythrokeratoderma v3.29 PERP Achchuthan Shanmugasundram Source Expert Review Green was added to PERP.
Source NHS GMS was added to PERP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ichthyosis and erythrokeratoderma v2.7 PERP Achchuthan Shanmugasundram edited their review of gene: PERP: Changed phenotypes to: Olmsted syndrome-2, MIM# 619208, MONDO:003091, Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO:0030941, Ichthyosis, MONDO:0019269, Alopecia universalis, congenital hypotrichosis
Ichthyosis and erythrokeratoderma v2.7 PERP Achchuthan Shanmugasundram Phenotypes for gene: PERP were changed from Olmsted syndrome-2, MIM# 619208, MONDO:003091; Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO:0030941; ichthyosis, MONDO:0019269 to Olmsted syndrome-2, MIM# 619208, MONDO:003091; Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO:0030941; Ichthyosis, MONDO:0019269
Ichthyosis and erythrokeratoderma v2.6 PERP Achchuthan Shanmugasundram Phenotypes for gene: PERP were changed from Olmsted syndrome-2, MIM# 619208, MONDO_003091; Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO_0030941; ichthyosis, MONDO:0019269 to Olmsted syndrome-2, MIM# 619208, MONDO:003091; Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO:0030941; ichthyosis, MONDO:0019269
Ichthyosis and erythrokeratoderma v2.5 PERP Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: PERP.
Ichthyosis and erythrokeratoderma v2.5 PERP Achchuthan Shanmugasundram Phenotypes for gene: PERP were changed from Erythrokeratoderma, no OMIM # yet to Olmsted syndrome-2, MIM# 619208, MONDO_003091; Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO_0030941; ichthyosis, MONDO:0019269
Ichthyosis and erythrokeratoderma v2.4 PERP Achchuthan Shanmugasundram Publications for gene: PERP were set to 31898316
Ichthyosis and erythrokeratoderma v2.3 PERP Achchuthan Shanmugasundram Mode of inheritance for gene: PERP was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ichthyosis and erythrokeratoderma v2.2 PERP Achchuthan Shanmugasundram Classified gene: PERP as Amber List (moderate evidence)
Ichthyosis and erythrokeratoderma v2.2 PERP Achchuthan Shanmugasundram Gene: perp has been classified as Amber List (Moderate Evidence).
Ichthyosis and erythrokeratoderma v2.1 PERP Achchuthan Shanmugasundram reviewed gene: PERP: Rating: GREEN; Mode of pathogenicity: None; Publications: 31898316, 30321533, 31361044, 34265120, 34863005, 32593191; Phenotypes: Olmsted syndrome-2, MIM# 619208, MONDO_003091, Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO_0030941, ichthyosis, MONDO:0019269, Alopecia universalis, congenital hypotrichosis; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ichthyosis and erythrokeratoderma v1.6 PERP Zornitza Stark edited their review of gene: PERP: Added comment: Four families reported with heterozygous variants and Olmsted syndrome-2 (OLMS2), which is characterised by mutilating hyperkeratotic skin lesions, primarily on the palms and soles, but also extending onto dorsal surfaces of the hands and feet and distal extremities. The lesions are progressive, becoming thicker with verrucous fissures on the palms and soles over time. In addition, affected individuals exhibit perioral hyperkeratosis, and may have lesions around other orifices as well, such as the nostrils, perineum, and anus. Most patients also have hyperkeratotic nails and light-colored woolly hair.

Two families reported with bi-allelic variants and Erythrokeratodermia variabilis et progressiva-7 (EKVP7), which is characterised by palmoplantar keratoderma that extends to the dorsal surface of the hands and feet (transgrediens), as well as erythematous annular skin lesions. Pruritis, woolly hair, and dystrophic nails may also be present.; Changed rating: GREEN; Changed publications: 31898316, 30321533, 31361044; Changed phenotypes: Olmsted syndrome 2, MIM# 619208, Erythrokeratodermia variabilis et progressiva 7, MIM# 619209; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Set current diagnostic: yes
Ichthyosis and erythrokeratoderma v1.3 PERP Zornitza Stark gene: PERP was added
gene: PERP was added to Ichthyosis and erythrokeratoderma. Sources: Literature
Mode of inheritance for gene: PERP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PERP were set to 31898316
Phenotypes for gene: PERP were set to Erythrokeratoderma, no OMIM # yet
Review for gene: PERP was set to AMBER
Added comment: One extended multiplex consanguineous family with Erythrokeratoderma (striking similarity to that observed in Perp −/− mice), and a novel homozygous variant (c.466G>A; p.Gly156Arg) in PERP that fully segregated with the phenotype. Functional analysis of patient‐ and control‐derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP. A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that recessive inheritance is also possible.
Sources: Literature