Genetics of kidney disorders in Phelan-McDermid syndrome: evidence from 357 registry participants.
Pediatr Nephrol
; 39(3): 749-760, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-37733098
ABSTRACT
BACKGROUND:
Phelan-McDermid syndrome (PMS) is a rare genetic disorder caused by SHANK3 pathogenic variants or chromosomal rearrangements affecting the chromosome 22q13 region. Previous research found that kidney disorders, primarily congenital anomalies of the kidney and urinary tract, are common in people with PMS, yet research into candidate genes has been hampered by small study sizes and lack of attention to these problems.METHODS:
We used a cohort of 357 people from the Phelan-McDermid Syndrome Foundation International Registry to investigate the prevalence of kidney disorders in PMS using a cross-sectional design and to identify 22q13 genes contributing to these disorders.RESULTS:
Kidney disorders reported included vesicoureteral reflux (n = 37), hydronephrosis (n = 36), dysplastic kidneys (n = 19), increased kidney size (n = 19), polycystic kidneys (15 cases), and kidney stones (n = 4). Out of 315 subjects with a 22q13 deletion, 101 (32%) had at least one kidney disorder, while only one out of 42 (2%) individuals with a SHANK3 pathogenic variant had a kidney disorder (increased kidney size). We identified two genomic regions that were significantly associated with having a kidney disorder with the peak associations observed near positions approximately 5 Mb and 400 Kb from the telomere.CONCLUSIONS:
The candidate genes for kidney disorders include FBLN1, WNT7B, UPK3A, CELSR1, and PLXNB2. This study demonstrates the utility of patient registries for uncovering genetic contributions to rare diseases. Future work should focus on functional studies for these genes to assess their potential pathogenic contribution to the different subsets of kidney disorders.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transtornos Cromossômicos
/
Doenças Renais Policísticas
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Pediatr Nephrol
Assunto da revista:
NEFROLOGIA
/
PEDIATRIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos