15 year old boy (patient II‐1)
Case#: Moore_2006_Family_1_Patient_II-1, male, 15 years old at time of report, national origin not mentioned
CasePresentingHPOs: HP:0011463 (Childhood onset), HP:0011109 (Chronic sinusitis), HP:0031353 (Otitis media with effusion), HP:0002837 (Recurrent bronchitis), HP:0100750 (Atelectasis), HP:0002110 (Bronchiectasis), HP:0006536 (Airway obstruction), HP:0005101 (High-frequency hearing impairment), HP:0012263 (Immotile cilia), HP:0012258 (Abnormal axonemal organization of respiratory motile cilia), HP:0012264 (Absent central microtubular pair morphology of respiratory motile cilia), HP:0012256 (Absent outer dynein arms), HP:0012257 (Absent inner dynein arms)
CaseHPOFreeText: The patient received a diagnosis of primary ciliary dyskinesia in early childhood, followed by retinitis pigmentosa diagnosed later in childhood. Atelectasis was severe and led to partial lobectomy at age 14 years. Microbiology detected Haemophilus influenzae. Biopsies showed both motile and immotile cilia.
CaseNotHPOs: HP:0002643 (Neonatal respiratory distress), HP:0012418 (Hypoxemia), HP:0030853 (Heterotaxy)
CaseNotHPOFreeText: N/A
CasePreviousTesting: Based on a family history consistent with X-linked inheritance, the patient and family members were subjected to segregation analysis using 4 microsatellite markers on the X chromosome. Genome-wide methods were not used for genotyping.
CaseMethod1: Sanger sequencing of PCR products from each of the 19 coding exons of RPGR, including the flanking intronic sequences
CaseMethod2: N/A
CaseGenotypingMethod: The patient and family members were subjected to segregation analysis using 4 microsatellite markers on the X chromosome. Sanger sequencing of PCR products from each of the 19 coding exons of RPGR, including the flanking intronic sequences, was then performed. Genome-wide methods were not used for genotyping.
Variant: The patient harbors the NM_001034853.2(RPGR):c.572_619+9del variant in the hemizygous state.
CAID: CA2573131867
gnomAD: This variant was not found in gnomAD v.2.1.1.
VariantEvidence: NM_001034853.2(RPGR):c.572_619+9del is a deletion variant spanning the function between exon 6 and intron 6. It has been shown to yield a shorter mRNA generated by the use of a cryptic splice donor site in exon 6 (Figure 4) that is predicted to trigger a frameshift and nonsense-mediated decay or disruption of the C-terminal 84% of the protein product.
CaseAddInfo: The proband is a member of Family 1, which has a pedigree shown in Figure 1. The patient's family includes a similarly affected brother and a mother diagnosed with retinitis pigmentosa, both harboring the RPGR variant of interest. Parents are reportedly non-consanguineous.
CasePMIDs: N/A