ORPHA: 55654; DO: 0110708;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q32.1 | Hypotrichosis 11 | 615059 | Autosomal dominant | 3 | SNRPE | 128260 |
A number sign (#) is used with this entry because of evidence that hypotrichosis-11 (HYPT11) is caused by heterozygous mutation in the SNRPE gene (128260) on chromosome 1q32.
Hypotrichosis-11 (HYPT11) is a form of isolated alopecia characterized by diffuse and progressive loss of hair starting in childhood. Affected individuals typically present with sparse to absent scalp hair, and may have brittle or absent eyebrows and eyelashes as well as sparse body hair, without hair shaft anomalies (summary by Pan et al., 2021).
For a general phenotypic description and a discussion of genetic heterogeneity of nonsyndromic hypotrichosis, see HYPT1 (605389).
Just et al. (1998) reported a large 4-generation Spanish family in which 8 affected members had hypotrichosis involving the scalp, eyebrows, and eyelashes, as well as axillary and body hair, but sparing the pubic hair. The hair, when present, was fair and of fine texture. There was variable severity of hypotrichosis among the affected members, with the 4-year-old proband and his 32-year-old mother having diffuse absence of scalp hair with scant eyelashes and eyebrows, whereas the proband's 2 cousins had total absence of hair since birth. The scalp, teeth, and nails showed no visible pathology, intelligence was normal, and there were no other associated anomalies. Hair plucked from 2 affected individuals showed no detectable alteration under light or scanning microscopy, and histologic examination of a scalp biopsy from 1 of the alopecic cousins showed follicles of vellus type.
Pan et al. (2021) reported 3 unrelated patients with hypotrichosis and mutation in the SNRPE gene. The first case was a 6-year-old Chinese girl with sparse scalp hair and a history of short brittle eyebrows and eyelashes since birth. She experienced a pronounced and progressive loss of hair from the scalp, eyebrows, and eyelashes after age 1.5 years, and exhibited a paucity of body hair as well. The second case was a 2.5-year-old Spanish boy who showed hypotrichosis from birth, and the third case was a 21-year-old Turkish woman with sparse hair and absent eyebrows. None of the patients exhibited microcephaly or impaired intellectual development. The authors noted that the patients exhibited wide phenotypic variation, like that seen in the originally reported HYPT11 patients.
The transmission pattern of HYPT11 in the family reported by Just et al. (1998) and Pasternack et al. (2013) was consistent with autosomal dominant inheritance.
The heterozygous mutation in the SNRPE gene that was identified in a patient (family 2) with HYPT11 by Pasternack et al. (2013) occurred de novo.
After excluding 7 loci known to be associated with hypotrichosis or alopecia in the Spanish family segregating autosomal dominant hypotrichosis reported by Just et al. (1998), Pasternack et al. (2013) performed genomewide linkage analysis and found evidence for linkage to chromosome 1q, obtaining a maximum lod score of 2.3 at D1S1660 (theta = 0). Genotyping of additional markers narrowed the candidate region to 21 Mbp, between D1S408 and D1S2141.
In the Spanish family with autosomal dominant hypotrichosis reported by Just et al. (1998), Pasternack et al. (2013) excluded 60 genes on chromosome 1q31-q34 by direct sequencing and then identified heterozygosity for a mutation in the start codon of SNRPE (128260.0001) that segregated with the disease. By sequencing SNRPE in additional patients in a hypotrichosis cohort, they detected the same mutation in a British girl, and also identified a missense mutation in a Tunisian patient (G45S; 128260.0002). Neither mutation was found in 880 German control chromosomes or 598 Spanish control chromosomes, and neither was present in the dbSNP or 1000 Genomes Project databases.
In 3 unrelated patients with hypotrichosis, Pan et al. (2021) identified heterozygosity for mutations in the SNRPE gene: a 21-year-old Turkish woman (case 3) carried the previously reported start codon variant c.1A-G (128260.0001), a 6-year-old Chinese girl (case 1) had a de novo splice site variant (128260.0003), and a 2.5-year-old Spanish boy (case 2) carried a de novo missense mutation (L74P; 128260.0004). Noting the ethnic diversity of their patients, the authors suggested that mutations in SNRPE are a relatively frequent occurrence.
Just, M., Ribera, M., Fuente, M. J., Bielsa, I., Ferrandiz, C. Hereditary hypotrichosis simplex. Dermatology 196: 339-342, 1998. [PubMed: 9621144] [Full Text: https://doi.org/10.1159/000017909]
Pan, C., Humbatova, A., Zheng, L., Cesarato, N., Grimm, C., Chen, F., Blaumeiser, B., Catalan-Lamban, A., Patino-Garcia, A., Fischer, U., Cheng, R., Li, Y., Yu, X., Yao, Z., Li, M., Betz, R. C. Additional causal SNRPE mutations in hereditary hypotrichosis simplex. Brit. J. Derm. 185: 439-441, 2021. [PubMed: 33792916] [Full Text: https://doi.org/10.1111/bjd.20089]
Pasternack, S. M., Refke, M., Paknia, E., Hennies, H. C., Franz, T., Schafer, N., Fryer, A., van Steensel, M., Sweeney, E., Just, M., Grimm, C., Kruse, R., Ferrandiz, C., Nothen, M. M., Fischer, U., Betz, R. C. Mutations in SNRPE, which encodes a core protein of the spliceosome, cause autosomal-dominant hypotrichosis simplex. Am. J. Hum. Genet. 92: 81-87, 2013. [PubMed: 23246290] [Full Text: https://doi.org/10.1016/j.ajhg.2012.10.022]