Biallelic variants in the ciliary gene TMEM67 cause RHYNS syndrome

被引：13

作者：

Brancati, Francesco ^{[1
,2
]}

Camerota, Letizia ^{[2
]}

Colao, Emma ^{[3
]}

Vega-Warner, Virginia ^{[4
]}

Zhao, Xiangzhong ^{[5
]}

Zhang, Ruixiao ^{[6
]}

Bottillo, Irene ^{[7
]}

Castori, Marco ^{[8
]}

Caglioti, Alfredo ^{[9
]}

Sangiuolo, Federica ^{[10
]}

Novelli, Giuseppe ^{[10
]}

Perrotti, Nicola ^{[11
]}

Otto, Edgar A. ^{[12
]}

Salvatore, Marco

De Stefano, Maria Chiara

Censi, Federica

Floridia, Giovanna

Brancati, Francesco ^{[1
,2
]}

Novelli, Giuseppe ^{[10
]}

Daina, Erica

Iatropoulos, Paraskevas

Ferlini, Alessandra

Neri, Marcella

Roccatello, Dario

Baldovino, Simone

Menegatti, Elisa

Bembi, Bruno

机构：

[1] Univ Aquila, Dept Life Hlth & Environm Sci, Laquila, Italy

[2] IRCCS, IDI, Lab Mol & Cell Biol, Rome, Italy

[3] Mater Domini Univ Hosp, Med Genet Unit, Catanzaro, Italy

[4] Univ Michigan, Sch Med, Dept Pediat & Communicable Dis, Div Nephrol, Ann Arbor, MI 48109 USA

[5] Qingdao Univ, Cent Lab, Affiliated Hosp, Qingdao, Peoples R China

[6] Qingdao Univ, Affiliated Hosp, Dept Nephrol, Qingdao, Peoples R China

[7] Sapienza Univ, San Camillo Forlanini Hosp, Dept Mol Med, Div Med Genet, Rome, Italy

[8] IRCCS Casa Sollievo Sofferenza, Div Med Genet, Foggia, Italy

[9] Mater Domini Univ Hosp, Nephrol & Dialysis Unit, Catanzaro, Italy

[10] Univ Roma Tor Vergata, Dept Biomed & Prevent, Rome, Italy

[11] Univ Catanzaro Magna Graecia, Dept Hlth Sci, Catanzaro, Italy

[12] Univ Michigan, Sch Med, Dept Internal Med, Div Nephrol, Ann Arbor, MI USA

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2018年 / 26卷 / 09期

关键词：

MECKEL-GRUBER-SYNDROME; GROWTH-HORMONE DEFICIENCY; CONGENITAL HEPATIC-FIBROSIS; JOUBERT-SYNDROME; RETINITIS-PIGMENTOSA; SKELETAL DYSPLASIA; COACH SYNDROME; MUTATIONS; MKS3; NEPHRONOPHTHISIS;

D O I：

10.1038/s41431-018-0183-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A rare syndrome was first described in 1997 in a 17-year-old male patient presenting with Retinitis pigmentosa, HYpopituitarism, Nephronophthisis and Skeletal dysplasia (RHYNS). In the single reported familial case, two brothers were affected, arguing for X-linked or recessive mode of inheritance. Up to now, the underlying genetic basis of RHYNS syndrome remains unknown. Here we applied whole-exome sequencing in the originally described family with RHYNS to identify compound heterozygous variants in the ciliary gene TMEM67. Sanger sequencing confirmed a paternally inherited nonsense c.622A > T, p.(Arg208*) and a maternally inherited missense variant c.1289A > G, p.(Asp430Gly), which perturbs the correct splicing of exon 13. Overall, TMEM67 showed one of the widest clinical continuum observed in ciliopathies ranging from early lethality to adults with liver fibrosis. Our findings extend the spectrum of phenotypes/syndromes resulting from biallelic TMEM67 variants to now eight distinguishable clinical conditions including RHYNS syndrome.

引用

页码：1266 / 1271

页数：6

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