BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare multisystem developmental disorder. In this study, we report the genetic causes and clinical manifestations in two Chinese families with BBS. MATERIALS AND METHODS: Two families were recruited in this study. Family A was a four-generation family with four affected and 15 unaffected members participating in the study, and family B was a consanguineous family with one affected and three unaffected members participating. Whole exome sequencing was performed in the two families, followed by a multistep bioinformatics analysis. Sanger sequencing was used to verify the variants and to perform a segregation analysis. Comprehensive ocular and systemic examinations were also conducted. RESULTS: Novel compound heterozygous variants c.235T > G (p.T79P) and c.534 + 1G > T were detected in the BBS2 gene in family A, and known homozygous variant c.748G > A (p.G250R) was detected in the MKKS gene in family B. Both families presented with retinitis pigmentosa; however, except for polydactyly, all other systemic manifestations were different. All of the affected family members in family A were overweight with a high body mass index (range from 26.5 to 41.9) and high blood pressure. Family A also presented with a delay in the onset of secondary sex characteristics and genital anomalies, while other systemic abnormalities were absent in family B. CONCLUSIONS: This study presents one family with two novel BBS2 variants, expanding the variant spectrum of BBS, and one family with a known homozygous MKKS variant. The different phenotypes seen between the families with BBS2 and MKKS variants will contribute to the literature and our overall understanding of BBS.
BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare multisystem developmental disorder. In this study, we report the genetic causes and clinical manifestations in two Chinese families with BBS. MATERIALS AND METHODS: Two families were recruited in this study. Family A was a four-generation family with four affected and 15 unaffected members participating in the study, and family B was a consanguineous family with one affected and three unaffected members participating. Whole exome sequencing was performed in the two families, followed by a multistep bioinformatics analysis. Sanger sequencing was used to verify the variants and to perform a segregation analysis. Comprehensive ocular and systemic examinations were also conducted. RESULTS: Novel compound heterozygous variants c.235T > G (p.T79P) and c.534 + 1G > T were detected in the BBS2 gene in family A, and known homozygous variant c.748G > A (p.G250R) was detected in the MKKS gene in family B. Both families presented with retinitis pigmentosa; however, except for polydactyly, all other systemic manifestations were different. All of the affected family members in family A were overweight with a high body mass index (range from 26.5 to 41.9) and high blood pressure. Family A also presented with a delay in the onset of secondary sex characteristics and genital anomalies, while other systemic abnormalities were absent in family B. CONCLUSIONS: This study presents one family with two novel BBS2 variants, expanding the variant spectrum of BBS, and one family with a known homozygous MKKS variant. The different phenotypes seen between the families with BBS2 and MKKS variants will contribute to the literature and our overall understanding of BBS.
Authors: Annie P Chiang; John S Beck; Hsan-Jan Yen; Marwan K Tayeh; Todd E Scheetz; Ruth E Swiderski; Darryl Y Nishimura; Terry A Braun; Kwang-Youn A Kim; Jian Huang; Khalil Elbedour; Rivka Carmi; Diane C Slusarski; Thomas L Casavant; Edwin M Stone; Val C Sheffield Journal: Proc Natl Acad Sci U S A Date: 2006-04-10 Impact factor: 11.205
Authors: Darryl Y Nishimura; Ruth E Swiderski; Charles C Searby; Erik M Berg; Amanda L Ferguson; Raoul Hennekam; Saul Merin; Richard G Weleber; Leslie G Biesecker; Edwin M Stone; Val C Sheffield Journal: Am J Hum Genet Date: 2005-10-26 Impact factor: 11.025
Authors: José L Badano; Stephen J Ansley; Carmen C Leitch; Richard Alan Lewis; James R Lupski; Nicholas Katsanis Journal: Am J Hum Genet Date: 2003-02-03 Impact factor: 11.025
Authors: Corinne Stoetzel; Virginie Laurier; Erica E Davis; Jean Muller; Suzanne Rix; José L Badano; Carmen C Leitch; Nabiha Salem; Eliane Chouery; Sandra Corbani; Nadine Jalk; Serge Vicaire; Pierre Sarda; Christian Hamel; Didier Lacombe; Muriel Holder; Sylvie Odent; Susan Holder; Alice S Brooks; Nursel H Elcioglu; Eduardo D Silva; Eduardo Da Silva; Béatrice Rossillion; Sabine Sigaudy; Thomy J L de Ravel; Richard Alan Lewis; Bruno Leheup; Alain Verloes; Patrizia Amati-Bonneau; André Mégarbané; Olivier Poch; Dominique Bonneau; Philip L Beales; Jean-Louis Mandel; Nicholas Katsanis; Hélène Dollfus Journal: Nat Genet Date: 2006-04-02 Impact factor: 38.330