| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Skeletal dysplasia v3.5 | HHAT | Eleanor Williams Tag Q4_21_rating was removed from gene: HHAT. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v3.5 | HHAT | Eleanor Williams changed review comment from: The rating of this gene has been updated to greenfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v3.5 | HHAT | Eleanor Williams commented on gene: HHAT: The rating of this gene has been updated to greenfollowing NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v3.4 | HHAT |
Eleanor Williams Source Expert Review Green was added to HHAT. Source NHS GMS was added to HHAT. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Skeletal dysplasia v2.162 | HHAT | Eleanor Williams Classified gene: HHAT as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.162 | HHAT | Eleanor Williams Added comment: Comment on list classification: Promotion from grey to amber but with a recommendation for green rating following GMS review. 3 cases reported with a skeletal dysplasia phenotype and variants in HHAT. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.162 | HHAT | Eleanor Williams Gene: hhat has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.161 | HHAT | Eleanor Williams Tag Q4_21_rating tag was added to gene: HHAT. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.161 | HHAT |
Eleanor Williams changed review comment from: Associated with Nivelon-Nivelon-Mabille syndrome #600092 (AR) in OMIM. PMID:24784881 - Callier et al 2014 - report a family with 2 siblings with Disorder of Sex Development (DSD) and chondrodysplasia (Nivelon-Nivelon-Mabille syndrome). The first sibling (46,XY karyotype) displayed severe dwarfism with generalized chondrodysplasia, a narrow, bell-shaped thorax, micromelia, brachydactyly, severe microcephaly (-7.5 SD at age 16 (PMID:15578577) with cerebellar vermis hypoplasia, facial anomalies, hypoplastic irides, and coloboma of both optic discs. Complete gonadal dysgenesis and intellectual disability is also noted. The second sibling (46,XX karyotype) had histologically normal ovaries and similar phenotypic abnormalities including severe dwarfism and generalized chondrodysplasia. Using WES a homozygous missense variant was found NM_001122834:c.860G>T:p.(Gly287Val) in HHAT in the first sibling which is in the conserved MBOAT domain. The parents were heterozygous. PMID:30912300 - Abdel-Salam et al 2019 - report two siblings with progressive microcephaly (-6 SD at age 6 and age 3 for the 2 siblings respectively), early infantile onset seizures, and cerebellar vermis hypoplasia but notably without dwarfism and gonadal dysgenesis. Skeletal x-rays of both siblings showed nlarged epiphyses and metaphyses, thinning of the lateral 1/3 of clavicles and trapezoidal vertebral bodies. WES found a homozygous missense (c.770T>C, p.[Leu257Pro]) HHAT which is in the conserved MBOAT domain. Both parents were heterozygous for the variant. PMID: 33749989 - Pande et al 2021 - report multiple malformations in three pregnancies with a novel biallelic in-frame deletion, c.365_367del; (p.Thr122del), in exon 5 of HHAT in the living proband. She shows severe microphthalmia, microcephaly (−8 SD head circumference at age 7), skeletal dysplasia (narrow bell-shaped tho-rax, short and angel-shaped epiphyses of hands and feet) and midfac eretrusion, short columella with a groove at the base, prominent ears, long philtrum, depressed nasal bridge, everted lower lip, and a singlec entral incisor. She also has complete sex reversal (karyotype of 46, XY, normal internal organs including uterus and ovaries.); to: Associated with Nivelon-Nivelon-Mabille syndrome #600092 (AR) in OMIM. PMID:24784881 - Callier et al 2014 - report a family with 2 siblings with Disorder of Sex Development (DSD) and chondrodysplasia (Nivelon-Nivelon-Mabille syndrome). The first sibling (46,XY karyotype) displayed severe dwarfism with generalized chondrodysplasia, a narrow, bell-shaped thorax, micromelia, brachydactyly, severe microcephaly (-7.5 SD at age 16 (PMID:15578577) with cerebellar vermis hypoplasia, facial anomalies, hypoplastic irides, and coloboma of both optic discs. Complete gonadal dysgenesis ( including normal external female genitalia, lack of pubertal development, primary amenorrhea, and hypergonadotrophic hypogonadism) and intellectual disability is also noted. The second sibling (46,XX karyotype) had histologically normal ovaries and similar phenotypic abnormalities including severe dwarfism and generalized chondrodysplasia. Using WES a homozygous missense variant was found NM_001122834:c.860G>T:p.(Gly287Val) in HHAT in the first sibling which is in the conserved MBOAT domain. The parents were heterozygous. They also found that mice lacking functional Hhat show a similar phenotype as the syndromic 46,XY DSD patient including testicular dysgenesis and skeletal defects. PMID:30912300 - Abdel-Salam et al 2019 - report two siblings with progressive microcephaly (-6 SD at age 6 and age 3 for the 2 siblings respectively), early infantile onset seizures, and cerebellar vermis hypoplasia but notably without dwarfism and gonadal dysgenesis. Skeletal x-rays of both siblings showed enlarged epiphyses and metaphyses, thinning of the lateral 1/3 of clavicles and trapezoidal vertebral bodies. Both sisters had a normal female karyotype (46, XX). WES found a homozygous missense (c.770T>C, p.[Leu257Pro]) HHAT which is in the conserved MBOAT domain. Both parents were heterozygous for the variant. PMID: 33749989 - Pande et al 2021 - report multiple malformations in three pregnancies with a novel biallelic in-frame deletion, c.365_367del; (p.Thr122del), in exon 5 of HHAT in the living proband. She shows severe microphthalmia, microcephaly (−8 SD head circumference at age 7), skeletal dysplasia (narrow bell-shaped tho-rax, short and angel-shaped epiphyses of hands and feet) and midfac eretrusion, short columella with a groove at the base, prominent ears, long philtrum, depressed nasal bridge, everted lower lip, and a singlec entral incisor. She also has complete sex reversal (karyotype of 46, XY, normal internal organs including uterus and ovaries.) |
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| Skeletal dysplasia v2.161 | HHAT | Eleanor Williams Phenotypes for gene: HHAT were changed from Nivelon-Nivelon-Mabille syndrome 600092 to Nivelon-Nivelon-Mabille syndrome, OMIM:600092 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.160 | HHAT | Eleanor Williams Publications for gene: HHAT were set to 24784881; 30912300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.159 | HHAT | Eleanor Williams reviewed gene: HHAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 24784881, 30912300, 33749989; Phenotypes: Nivelon-Nivelon-Mabille syndrome, OMIM:600092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.34 | HHAT |
Zornitza Stark gene: HHAT was added gene: HHAT was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: HHAT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HHAT were set to 24784881; 30912300 Phenotypes for gene: HHAT were set to Nivelon-Nivelon-Mabille syndrome 600092 Review for gene: HHAT was set to AMBER Added comment: Two unrelated families reported. Clinical features include progressive microcephaly, cerebellar vermis hypoplasia, and skeletal dysplasia. Variable features include infantile-onset seizures, dwarfism, generalized chondrodysplasia, and micromelia. Sources: Literature |
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