In other species: horse

Categories: Endocrine / exocrine gland phene (incl mammary gland)

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 113700 (trait) , 104350 (trait) , 616001 (trait)

Mendelian trait/disorder: unknown

Disease-related: yes

Year key variant first reported: 2022

Inheritance: Jacinto et al. (2022) "suspected that the identified variant in SGSH either occurred post-zygotically in the developing embryo or was inherited from a mosaic parent. Unfortunately, no biological samples were available from the parents."

Molecular basis: Jacinto et al. (2022) reported that "Whole genome sequencing (WGS) was performed using genomic DNA obtained from ear tissue from the [affected] calf. . . . Variant filtering did not reveal any private homozygous protein-changing variants present in the genome of the affected calf, making a possible recessive inheritance unlikely. Assuming that a spontaneous mutation affecting a protein-coding gene is the cause, filtering for private heterozygous coding variants present in the calf’s genome allowed the identification of six variants with a predicted moderate or high impact. . . . These variants were absent from a total of 5365 controls and a single variant affects SGSH, a putative candidate gene for the observed congenital anomaly. This heterozygous variant at chr19:52427490C>T represents a missense variant in SGSH exon 4 (NM_001102189.2: c.425C>T . . . The encoded amino acid of SGSH is predicted to be altered at codon 142 (NP_001095659.2: p.Thr142Met) located in the N-sulphoglucosamine sulphohydrolase domain. The substitution of threonine to methionine affects an amino acid that is highly conserved in all species . . . and has been predicted to be harmful using three different tools (Provean, −4.729; PhD-SNP, 50%; SIFT, 79%)." Consistent with the question mark in the title, the authors were cautious in concluding that "the identified missense variant might be considered as a possible cause for the observed congenital anomaly, although this gene has not been associated with syndromic forms of amastia in mammals, including humans. However, the possible role of SGSH in the origin of mammary gland developmental defects needs to be confirmed in future research."

Clinical features: Jacinto et al. (2022): "A 5-days-old female purebred Original Braunvieh female calf was referred owing to a congenital absence of teats and cleft palate".

Pathology: Jacinto et al. (2022): "Gross pathology revealed the entire absence of the udder including teats, complete palatoschisis affecting both soft and hard palate, hepatomegaly, corneal opacity and an open vulva".

Breed: Original Schweizer Braunvieh, Switzerland (Cattle) (VBO_0003764).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).