An Atypical Presentation of a Male with Oral-Facial-Digital Syndrome Type 1 Related Ciliopathy

Sharma, Sheena; Kalish, Jennifer M.; Goldberg, Ethan M.; Reynoso, Francis Jeshira; Pradhan, Madhura

doi:10.1155/2016/3181676

Cited by 9 publications

(10 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sharma et al reported an atypical presentation of OFD1 mutation in a male patient without the classical OFD1 phenotype. This patient presented ESRD without any evidence of polycystic kidney disease [16]. The spectrum of OFD1 mutations in males reported previously is summarized in Table 1.…”

Section: Discussionmentioning

confidence: 78%

Clinical spectrum of male patients with OFD1 mutations

et al. 2018

View full text Add to dashboard Cite

Oral-facial-digital syndrome type 1 (OFD1) is a ciliopathy characterized by oral, facial, and digital malformations that are often accompanied by polycystic lesion of the kidney and central nervous involvement. OFD1 shows an X-linked recessive inheritance caused by mutation in the OFD1 gene (Xp22.2). The disease is generally considered embryonic lethal for hemizygous males. However, males with OFD1 mutations were recently reported. Here, we report four additional Japanese male patients with OFD1 variants and describe the variable clinical manifestation and disease severity among the four patients. Patient 1 with pathogenic indels including a 19-bp deletion and 4-bp insertion (c.2600-18_2600delinsACCT) had end-stage renal disease (ESRD) with bilateral cystic kidneys and sensory hearing loss. He showed neither intellectual disability nor facial or digital dysmorphism. Patient 2 with a missense variant in exon 7 (c.539A>T, p.Asp180Val) presented head circumference enlargement, brachydactyly, high-arched palate, micropenis, severe global developmental delay, and ESRD. Patient 3 had a single base substitution at the splice donor site of intron 16 (c.2260+2T>G) causing a 513-bp deletion at the transcript level. The patient had chronic kidney disease and speech delay, but no oral, facial, or digital dysmorphism. 4 His uncle (patient 4) carried the same OFD1 variant and showed ESRD with extra-renal malformations including obesity and micropenis, which was previously diagnosed as Bardet-Biedl syndrome. The OFD1 mutations were not lethal in these four male patients, likely because the three mutations were in-frame or missense. This report provided insights into the onset mechanism and phenotype-genotype association in patients with OFD1 mutations.

show abstract

Section: Discussionmentioning

confidence: 78%

Clinical spectrum of male patients with OFD1 mutations

et al. 2018

View full text Add to dashboard Cite

show abstract

“…OFD1 variants have previously been reported in association with inherited renal cystic disease, with hypertension ( 22 ). Sharma et al described an XY male with a partial deletion of the OFD1 gene associated with hypogonadism ( 23 ).…”

Section: Resultsmentioning

confidence: 99%

Peripheral Precocious Puberty of Ovarian Origin in a Series of 18 Girls: Exome Study Finds Variants in Genes Responsible for Hypogonadotropic Hypogonadism

2021

View full text Add to dashboard Cite

Background: Peripheral precocious puberty of ovarian origin is a very rare condition compared to central form. It may be associated with an isolated ovarian cyst (OC). The causes of OC in otherwise healthy prepubertal girls is currently unknown.Methods: Exome sequencing was performed on a cohort of 18 unrelated girls presenting with prenatal and/or prepubertal OC at pelvic ultrasonography. The presenting symptom was prenatal OC in 5, breast development in 7 (with vaginal bleeding in 3) and isolated vaginal bleeding in 6. All had OC ≥ 10 mm. The girls had no other anomalies. Four patients had a familial history of ovarian anomalies and/or infertility.Results: In 9 girls (50%), candidate or known pathogenic variants were identified in genes associated with syndromic and non-syndromic forms of hypogonadotropic hypogonadism including PNPLA6, SEMA3A, TACR3, PROK2, KDM6A, KMT2D, OFD1, GNRH1, GNRHR, GLI3, INSR, CHD7, CDON, RNF216, PROKR2, GLI3, LEPR. Basal plasma concentrations of gonadotropins were undetectable and did not increase after gonadotropin-releasing hormone test in 3 of them whilst 5 had prepubertal values. The plasma estradiol concentrations were prepubertal in 6 girls, high (576 pmol/L) in one and not evaluated in 2 of them.Conclusions: In the first study reporting exome sequencing in prepubertal OC, half of the patients with OC carry either previously reported pathogenic variants or potentially pathogenic variants in genes known to be associated with isolated or syndromic forms of congenital hypogonadotropic hypogonadism. Functional studies and studies of other cohorts are recommended to establish the causality of these variants.

show abstract

“…In spite of autosomal dominant polycystic kidney disease (ADPKD), cysts in OFDS I originate from glomeruli rather than renal tubules. Additionally, size of cysts are not so large and overall renal size is not enlarged as in ADPKD (2). Renal insufficiency has been reported in OFDS primarily due to polycystic kidney disease.…”

Section: Discussionmentioning

confidence: 97%

“…Two of those types (OFDS I and OFDS IV) are associated with miscellaneous phenotypes and organ involvements that could overlap with each other in some presentations. OFDS type I is the most frequent type with estimated incidence of 1:50 000 -1:250 000 live births (2). It may occur in 1.5:1000 patients with cleft lip, cleft palate or both.…”

Section: Discussionmentioning

confidence: 99%