Data from: Biallelic missense variants in human GPN2 result in Perrault syndrome
Data files
May 27, 2026 version files 5.11 MB
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File1_Figure_1.tif
2.78 MB
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File2_Figure_2.tif
2.32 MB
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File3_Table_1.csv
2.15 KB
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File4_Table_2.csv
2 KB
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File5_Table_3.csv
593 B
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README.md
6.61 KB
Abstract
Perrault syndrome is a rare autosomal recessive condition characterized by bilateral sensorineural hearing loss and ovarian insufficiency. Three families were ascertained segregating Perrault syndrome. Using SNP genotyping, the phenotype was mapped to chromosome 1 and a LOD score of at least 6.03 was calculated. After SNP genotyping and exome sequencing, homozygous variants of GPN2 were identified and validated by Sanger sequencing. Audiograms from several affected individuals of Family 1 (PKDF1779) show significant hearing loss as shown in Figure 1 below. Figure 2 shows the results of SNP genotyping and Table 1 provides the data used for LOD score calculations. Clinical and biochemical data are provided in Tables 2 and 3. The bilaterally deaf female individuals have elevated plasma levels of follicular stimulating hormone (FSH) and luteinizing hormone (LH), and reduced estradiol levels, indicative of Perrault syndrome.
Dataset DOI: 10.5061/dryad.pnvx0k736
Description of the data and file structure
This folder contains data files for the article:
Thomas B. Smith, Rabia Faridi, Leigh A.M. Demain, Sayaka Inagaki, Yasuko Ishibashi, Huw B. Thomas, Inna A. Belyantseva, Alessandro Rea, King Lam Lai, Arshia Maqbool, Bushra Rauf, Muhammad Asad Usmani, Alejandro A. Schäffer, Robert J. Morell, Andrew Green, Sondhya Ghedia, Mathilda Wilding, Robin Hay, Yuliya Sokolova, Gavin P. Riordan, Isabelle Schrauwen, Khurram Liaqat, Saima Riazuddin, Zubair M. Ahmed, Wade W. Chien, Langping He, Amanda McGovern, Helen Byers, Glenda M. Beaman, Wasim Ahmad, Suzanne M. Leal, Robert W. Taylor, Sheikh Riazuddin, Raymond T. O’Keefe, Thomas B. Friedman, William G. Newman. “Biallelic missense variants in human GPN2 result in Perrault syndrome”. The American Journal of Human Genetics, under revision, AJHG-S-26-00345-3
This dataset contains good quality unpublished data collected by the Laboratory of Molecular Genetics, National Institute on Deafness and Communication Disorders, National Institutes of Health, USA and Manchester Centre for Genomic Medicine, St Mary’s Hospital, University of Manchester, associated with published data in The American Journal of Human Genetics (under revision, AJHG-S-26-00345-3). If you use data from this dataset, citation of the associated publication would be appreciated.
Perrault syndrome is a rare autosomal recessive condition characterized by bilateral sensorineural hearing loss and ovarian insufficiency. Three families were ascertained segregating Perrault syndrome. Using SNP genotyping, the phenotype was mapped to chromosome 1 and a LOD score of at least 6.03 was calculated. After SNP genotyping and exome sequencing, homozygous variants of GPN2 were identified and validated by Sanger sequencing. Audiograms from several affected individuals of Family 1 (PKDF1779) show significant hearing loss as shown in Figure 1 below. Figure 2 shows the results of SNP genotyping and Table 1 provides the data used for LOD score calculations. Clinical and biochemical data are provided in Tables 2 and 3. The bilaterally deaf female individuals have elevated plasma levels of follicular stimulating hormone (FSH) and luteinizing hormone (LH), and reduced estradiol levels, indicative of Perrault syndrome.
Files and variables
File1_Figure_1.tif
Description: All available audiograms for affected and unaffected individuals in Family 1 (PKDF1779). Red line represents air conduction hearing levels (dB) in the right ear at selected audible frequencies (Hertz) labelled with circles. The blue line represents air conduction hearing levels in the left ear, labelled with crosses. X-axis represents pure-tone frequencies increasing from left to right, y-axis represents decibel level of pure-tone stimuli. 25–40 dB = mild hearing loss, 40–55 dB = moderate, 55–70 dB = moderate-severe, 70–90 dB = severe, and 90–120 dB = profound hearing loss.
File2_Figure_2.tif
Description: Infinium Global Diversity Array-8 v1.0 microarray data for seven affected and six unaffected individuals from Family 1 (PKDF1779). “Common homozygous” genotype calls (AA or BB) within chromosome 1 (1q21.3) are visualized in black. “Rare homozygous” and “heterozygous calls” are shown in yellow, whilst “no calls” appear in grey (especially at the centromere). The large region of homozygosity in Family 1 (PKDF1779) and F3:II-2 is emphasized by the red boxes, and the approximate location of GPN2 in the magnified image is highlighted in red. The shared region of homozygosity individuals from Families F2 and F3 has its start point at 26,716,136Mb (rs9438620), and its end point at 27,378,312Mb (rs17162431), which is an approximate 662kb region of homozygosity (GRCh.p13.1 assembly), indicating a common haplotype. A smaller shared region of homozygosity from seven affected individuals from Family 1 (PKDF1779), IV:2, IV:3, IV:4, IV:5, IV:6, V:3, V:4 (genotypes indicated in the red box) has its endpoints at 26,854,238Mb (rs737524) and 26,888,688Mb (rs34460334) encompassing an approximately 34kb region. That smaller region contains three genes NM_032283.3: ZDHHC18, NM_006142.5: SFN, and GPN2. Coding exons of these genes were visualized by Integrative Genome Viewer to confirm adequate sequence coverage. Data presented using AutoSNPa (http://dna-leeds.co.uk/autosnpa/, GRCh37.p13).
File3_Table_1.csv
Description: Single-marker LOD scores for Family 1 (PKDF1779). There are 351 perfect markers on chromosome 1 from rs2811956 at position 23630828 (GRCh38 assembly) through rs12130968 at position 34325265. This interval includes GPN2. Among these, 47 markers were selected at which to compute a single-marker score. The scores at a recombination fraction of 0 between marker and disease locus are either 4.57 or 4.39. The variation in the LOD scores at different markers is due to the decision to require only that the genotypes of the unaffected individuals differ from the genotype of the affected individuals. However, the unaffected genotypes can vary between the two alternatives so long as the rules of inheritance are not violated. The asymptotic multi-marker score, as the frequency of the disease-associated haplotype decreases to 0, is at least 6.03.
File4_Table_2.csv
Description: Phenotypic and biochemical summary of individuals with GPN2 biallelic variants associated with Perrault Syndrome as described in Smith and Faridi et al 2026 AJHG. Hormone levels shown are before any replacement treatment was initiated. FSH, follicle stimulating hormone, LH, luteinizing hormone, N/A, not available.
File5_Table_3.csv
Description: Biochemical profile of Family 1 (PKDF1779) affected females and associated female reference ranges. Red font indicates abnormal readings. FSH = follicle-stimulating hormone, LH = luteinizing hormone, T3 = triiodothyronine, T4 = thyroxine, TSH = thyroid-stimulating hormone.
Human subjects data
All study subjects or their legal guardians provided written informed consent in accordance with local regulations. Ethical approval for this study was granted by the National Health Service Ethics Committee (16/WA/0017) and University of Manchester, by the Lahore Pakistan institutional review board (IRB), the IRB of the National Institutes of Health, USA (OH93-DC-0016).