Two novel truncating variants of the ASPM gene identified in a nonconsanguineous Chinese family associated with primary microcephaly
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Two novel truncating variants of the ASPM gene identified in a nonconsanguineous Chinese family associated with primary microcephaly. / Xu, Shuqin; Zhang, Wenqian; Zhou, Rui; Huang, Hui; Chen, Wei; Xiang, Wenhao; Liu, Limei; Song, Jieping.
I: Clinical Dysmorphology, Bind 31, Nr. 1, 2022, s. 1-5.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Two novel truncating variants of the ASPM gene identified in a nonconsanguineous Chinese family associated with primary microcephaly
AU - Xu, Shuqin
AU - Zhang, Wenqian
AU - Zhou, Rui
AU - Huang, Hui
AU - Chen, Wei
AU - Xiang, Wenhao
AU - Liu, Limei
AU - Song, Jieping
PY - 2022
Y1 - 2022
N2 - Primary autosomal recessive microcephaly 5 (MCPH5) is a rare neurodevelopmental disorder with a relatively high incidence in regions where consanguineous marriage is widely practiced; So far, only a few MCPH5 cases have been reported from China. Here, we report clinical and molecular characteristics of two Chinese MCPH5 patients, a 24-year-old woman proband and her brother, a 19-year-old man, from a nonconsanguineous family. Main manifestations in the proband were small head circumference, premature closure of fontanelles, impaired concentration and moderate intellectual disability. The proband's brother had similar symptoms, but he was hyperactive and had a more severe sloping forehead. Brain imaging revealed global reduction in brain size, especially in the frontal lobes bilaterally and anterior horns of lateral ventricles. Sequencing results revealed that both patients carried a novel nonsense variant p.Tyr2004* (c.6012_6013delTA) and a novel frameshift variant p.Arg2005Serfs*48 (c.6015_6016delGG) in the ASPM gene. These variants were interpreted to be pathogenic in the in-silico analysis. Our findings help to expand the mutation spectrum of ASPM and provide new opportunities for assisting the traditional clinical diagnosis on the cases with atypical characteristics.
AB - Primary autosomal recessive microcephaly 5 (MCPH5) is a rare neurodevelopmental disorder with a relatively high incidence in regions where consanguineous marriage is widely practiced; So far, only a few MCPH5 cases have been reported from China. Here, we report clinical and molecular characteristics of two Chinese MCPH5 patients, a 24-year-old woman proband and her brother, a 19-year-old man, from a nonconsanguineous family. Main manifestations in the proband were small head circumference, premature closure of fontanelles, impaired concentration and moderate intellectual disability. The proband's brother had similar symptoms, but he was hyperactive and had a more severe sloping forehead. Brain imaging revealed global reduction in brain size, especially in the frontal lobes bilaterally and anterior horns of lateral ventricles. Sequencing results revealed that both patients carried a novel nonsense variant p.Tyr2004* (c.6012_6013delTA) and a novel frameshift variant p.Arg2005Serfs*48 (c.6015_6016delGG) in the ASPM gene. These variants were interpreted to be pathogenic in the in-silico analysis. Our findings help to expand the mutation spectrum of ASPM and provide new opportunities for assisting the traditional clinical diagnosis on the cases with atypical characteristics.
KW - ASPM
KW - neurodevelopmental disorder
KW - primary autosomal recessive microcephaly 5
KW - ABNORMAL SPINDLE PROTEIN
KW - MUTATION
KW - WDR62
KW - MCPH
U2 - 10.1097/MCD.0000000000000395
DO - 10.1097/MCD.0000000000000395
M3 - Journal article
C2 - 34693918
VL - 31
SP - 1
EP - 5
JO - Clinical Dysmorphology
JF - Clinical Dysmorphology
SN - 0962-8827
IS - 1
ER -
ID: 287069534